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  • 1.
    Bahnasawy, Salma M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Skorup, Paul
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Hanslin, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Friberg, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Nielsen, Elisabet I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Predicting cytokine kinetics during sepsis; a modelling framework from a porcine sepsis model with live Escherichia coli2023In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 169, article id 156296Article in journal (Refereed)
    Abstract [en]

    Background: Describing the kinetics of cytokines involved as biomarkers of sepsis progression could help to optimise interventions in septic patients. This work aimed to quantitively characterise the cytokine kinetics upon exposure to live E. coli by developing an in silico model, and to explore predicted cytokine kinetics at different bacterial exposure scenarios.

    Methods: Data from published in vivo studies using a porcine sepsis model were analysed. A model describing the time courses of bacterial dynamics, endotoxin (ETX) release, and the kinetics of TNF and IL-6 was developed. The model structure was extended from a published model that quantifies the ETX-cytokines relationship. An external model evaluation was conducted by applying the model to literature data. Model simulations were performed to explore the sensitivity of the host response towards differences in the input rate of bacteria, while keeping the total bacterial burden constant.

    Results: The analysis included 645 observations from 30 animals. The blood bacterial count was well described by a one-compartment model with linear elimination. A scaling factor was estimated to quantify the ETX release by bacteria. The model successfully described the profiles of TNF, and IL-6 without a need to modify the ETXcytokines model structure. The kinetics of TNF, and IL-6 in the external datasets were well predicted. According to the simulations, the ETX tolerance development results in that low initial input rates of bacteria trigger the lowest cytokine release.

    Conclusion: The model quantitively described and predicted the cytokine kinetics triggered by E. coli exposure. The host response was found to be sensitive to the bacterial exposure rate given the same total bacterial burden.

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  • 2.
    Bülow Anderberg, Sara
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Luther, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Berglund, Malin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Increased levels of plasma cytokines and correlations to organ failure and 30-day mortality in critically ill Covid-19 patients2021In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 138, article id 155389Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The infection caused by SARS CoV-2 has been postulated to induce a cytokine storm syndrome that results in organ failure and even death in a considerable number of patients. However, the inflammatory response in Corona virus disease-19 (Covid-19) and its potential to cause collateral organ damage has not been fully elucidated to date. This study aims to characterize the acute cytokine response in a cohort of critically ill Covid-19 patients.

    METHOD: 24 adults with PCR-confirmed Covid-19 were included at time of admission to intensive care a median of eleven days after initial symptoms. Eleven adult patients admitted for elective abdominal surgery with preoperative plasma samples served as controls. All patients were included after informed consent was obtained. 27 cytokines were quantified in plasma. The expression of inflammatory mediators was then related to routine inflammatory markers, SAPS3, SOFA score, organ failure and 30-day mortality.

    RESULTS: A general increase in cytokine expression was observed in all Covid-19 patients. A strong correlation between respiratory failure and IL-1ra, IL-4, IL-6, IL-8 and IP-10 expression was observed. Acute kidney injury development correlated well with increased levels of IL-1ra, IL-6, IL-8, IL-17a, IP-10 and MCP-1. Generally, the cohort demonstrated weaker correlations between cytokine expression and 30-day mortality out of which IL-8 showed the strongest signal in terms of mortality.

    CONCLUSION: The present study found that respiratory failure, acute kidney injury and 30-day mortality in critically ill Covid-19 patients are associated with moderate increases of a broad range of inflammatory mediators at time of admission.

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  • 3.
    Franzén, Stephanie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Semenas, Egidijus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Plasma cytokine levels in spinal surgery with sevoflurane or total intravenous propofol anesthesia: A post hoc analysis of a randomized controlled trial2023In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 169, article id 156290Article in journal (Refereed)
    Abstract [en]

    Surgical tissue trauma stimulates an inflammatory response resulting in increased levels of cytokines which could contribute to acute kidney injury (AKI). It is not clear if anesthetic modality affects this response. We aimed to investigate the role of anesthesia in a healthy surgical population on the inflammatory response and the correlation to plasma creatinine. This study is a post hoc analysis of a published randomized clinical trial. We analyzed plasma from patients who underwent elective spinal surgery randomized to either total intravenous propofol anesthesia (n = 12) or sevoflurane anesthesia (n = 10). The plasma samples were collected before anesthesia, during anesthesia, and 1 h after surgery. Plasma cytokine levels after surgery were analyzed for correlations with duration of surgical insult and change in plasma creatinine concentration. The cytokine interleukin-6 (IL-6) was increased after surgery compared with preoperatively. IL-6 was higher in the sevoflurane group than the propofol group after surgery. No patient developed AKI, but plasma creatinine was increased postoperatively in the sevoflurane group. There was a significant association between surgical time and plasma IL-6 postoperatively. No significant correlation between change in plasma creatinine and IL-6 was detected. The cytokines IL-4, IL-13, Eotaxin, Interferon γ-Induced Protein 10 (IP-10), Granulocyte Colony-Stimulating Factor (G-CSF), Macrophage Inflammatory Protein-1β (MIP-1β), and Monocyte Chemoattractant Protein 1 (MCP-1) were lower postoperatively than before surgery independent of anesthetic modality. This post hoc analysis revealed that plasma IL-6 was increased after surgery and more so in the sevoflurane group than the propofol group. Postoperative plasma IL-6 concentration was associated with surgical time.

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  • 4.
    Gradin, Anna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Andersson, Hanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Luther, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bülow Anderberg, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Åberg, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology.
    Urinary cytokines correlate with acute kidney injury in critically ill COVID-19 patients2021In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 146, article id 155589Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Acute kidney injury is common in COVID-19 patients admitted to the ICU. Urinary biomarkers are a non-invasive way of assaying renal damage, and so far, urinary cytokines are not fully investigated. The current study aimed to assess urinary cytokine levels in COVID-19 patients.

    METHODS: Urine was collected from COVID-19 patients (n = 29) in intensive care and compared to a preoperative group of patients (n = 9) with no critical illness. 92 urinary cytokines were analyzed in multiplex using the Olink Target 96 inflammation panel and compared to clinical characteristics, and urinary markers of kidney injury.

    RESULTS: There were strong correlations between proinflammatory cytokines and between urinary cytokines and urinary kidney injury markers in 29 COVID-19 patients. Several cytokines were correlated to kidney injury, 31 cytokines to AKI stage and 19 cytokines correlated to maximal creatinine.

    CONCLUSIONS: Urinary inflammatory cytokines from a wide range of immune cell lineages were significantly upregulated during COVID-19 and the upregulation correlated with acute kidney injury as well as urinary markers of kidney tissue damage.

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  • 5.
    Khamisi, Selwan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Thulin, Måns
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Increased plasma levels of soluble programmed death ligand 1 (sPD-L1) and fibroblast growth factor 23 (FGF-23) in patients with Graves' ophthalmopathy in comparison to hyperthyroid patients without Graves' ophthalmopathy.2023In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 169, p. 156269-, article id 156269Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Management of Graves' ophthalmopathy (GO) is still a challenge in Graves' disease (GD). Moreover, 40% of GD patients show radiological muscle enlargement without clinically apparent GO. Delayed treatment of GO may lead to deterioration in prognosis.

    METHODS: Thirty GD patients with overt hyperthyroidism were included in this study, 17 of whom either had GO at diagnosis or developed GO during the study period. Samples were collected at the beginning of the study, at 6 months, and at 24 months. Plasma samples were analyzed for 92 cytokines using the Olink Target 96 inflammation panel.

    RESULTS: After adjustment for multiplicity testing using the false discovery rate approach, soluble programmed death ligand 1 (sPD-L1) and fibroblast growth factor 23 (FGF-23) were significantly elevated in GO patients.

    CONCLUSION: Using a broad cytokine panel we show that patients with Graves' ophthalmopathy have elevated PD-L1 and FGF-23 levels. The findings support previous suggestions that PD-L1 may serve as a treatment target.

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  • 6. Kolosenko, Iryna
    et al.
    Edsbacker, Elin
    Fryknäs, Mårten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Johnsson, Per
    Grander, Dan
    Tamm, Katja Pokrovskaja
    Lindera, Stig
    De Milito, Angelo
    Cell crowding results in accumulation of interferon-stimulated genes independently of STAT12013In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 63, no 3, p. 278-278Article in journal (Other academic)
  • 7.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Anne-Li
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bodolea, Constantin
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Thulin, Måns
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    The body mass index (BMI) is significantly correlated with levels of cytokines and chemokines in cerebrospinal fluid2015In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 76, no 2, p. 514-518Article in journal (Refereed)
    Abstract [en]

    Cytokines and chemokines regulate many functions in the body including the brain. The interactions between adipose tissue and the central nervous system (CNS) are important for the regulation of energy balance. CNS function is also influenced by age. The aim of the present study was to investigate the effects of body mass index (BMI) and age on cytokine and chemokine levels in cerebrospinal fluid. Cerebrospinal fluid samples (n=89) were collected from patients undergoing routine surgical procedures. The samples were analyzed using the multiplex proximity extension assay (PEA) in which 92 different cytokines are measured simultaneously using minute sample volume. We found no significant correlations between age and cytokine levels for any of the studied markers. In contrast, at a false discovery rate of 10%, 19 markers were significantly associated with BMI (in decreasing significance: FGF-5, ADA, Beta-NGF, CD40, IL-10RB, CCL19, TGF-alpha, SIRT2, TWEAK, SCF, CSF-1, 4E-BP1, DNER, LIF-R, STAMPB, CXCL10, CXCL6, VEGF-A and CX3CL1). This study reveals a clear effect of BMI on cytokine and chemokine levels in cerebrospinal fluid.

  • 8.
    McLeod, Olga
    et al.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden..
    Silveira, Angela
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden..
    Valdes-Marquez, Elsa
    Univ Oxford, CTSU Nuffield Dept Populat Hlth, Oxford, England..
    Bjorkbacka, Harry
    Lund Univ, Expt Cardiovasc Res Unit, Dept Clin Sci Malmo, Malmo, Sweden..
    Almgren, Peter
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Gertow, Karl
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden..
    Gadin, Jesper R.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden..
    Backlund, Alexandra
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden..
    Sennblad, Bengt
    Karolinska Inst, Cardiovasc Med Unit, Dept Med, Sci Life Lab, S-17176 Stockholm, Sweden..
    Baldassarre, Damiano
    Univ Milan, Dipartimento Sci Farmacol & Biomol, I-20122 Milan, Italy.;IRCCS, Ctr Cardiol Monzino, Milan, Italy..
    Veglia, Fabrizio
    IRCCS, Ctr Cardiol Monzino, Milan, Italy..
    Humphries, Steve E.
    UCL, Ctr Cardiovasc Genet, London WC1E 6BT, England..
    Tremoli, Elena
    Univ Milan, Dipartimento Sci Farmacol & Biomol, I-20122 Milan, Italy.;IRCCS, Ctr Cardiol Monzino, Milan, Italy..
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-17176 Stockholm, Sweden..
    Nilsson, Jan
    Lund Univ, Expt Cardiovasc Res Unit, Dept Clin Sci Malmo, Malmo, Sweden..
    Melander, Olle
    Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden..
    Hopewell, Jemma C.
    Univ Oxford, CTSU Nuffield Dept Populat Hlth, Oxford, England..
    Clarke, Robert
    Univ Oxford, CTSU Nuffield Dept Populat Hlth, Oxford, England..
    Bjorck, Hanna M.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden..
    Öhrvik, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden..
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, S-17176 Stockholm, Sweden..
    Genetic loci on chromosome 5 are associated with circulating levels of interleukin-5 and eosinophil count in a European population with high risk for cardiovascular disease2016In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 81, p. 1-9Article in journal (Refereed)
    Abstract [en]

    IL-5 is a Th2 cytokine which activates eosinophils and is suggested to have an atheroprotective role. Genetic variants in the IL5 locus have been associated with increased risk of CAD and ischemic stroke. In this study we aimed to identify genetic variants associated with IL-5 concentrations and apply a Mendelian randomisation approach to assess IL-5 levels for causal effect on intima-media thickness in a European population at high risk of coronary artery disease. We analysed SNPs within robustly associated candidate loci for immune, inflammatory, metabolic and cardiovascular traits. We identified 2 genetic loci for IL-5 levels (chromosome 5, rs56183820, BETA = 0.11, P = 6.73E(-5) and chromosome 14, rs4902762, BETA = 0.12, P= 5.76E(-6)) and one for eosinophil count (rs72797327, BETA = -0.10, P = 1.41E(-6)). Both chromosome 5 loci were in the vicinity of the IL5 gene, however the association with IL-5 levels failed to replicate in a meta-analysis of 2 independent cohorts (rs56183820, BETA = 0.04, P= 0.2763, I-2 = 24, I-2 - P = 0.2516). No significant associations were observed between SNPs associated with IL-5 levels or eosinophil count and IMT measures. Expression quantitative trait analyses indicate effects of the IL-5 and eosinophil-associated SNPs on RAD50 mRNA expression levels (rs12652920 (r2 = 0.93 with rs56183820) BETA = -0.10, P = 8.64E(-6) and rs11739623 (r2 = 0.96 with rs72797327) BETA = -0.23, P = 1.74E(-29), respectively). Our data do not support a role for IL-5 levels and eosinophil count in intima-media thickness, however SNP5 associated with IL-5 and eosinophils might influence stability of the atherosclerotic plaque via modulation of RAD50 levels.

  • 9.
    Melhus, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ryan, Allen F.
    Effects of amoxicillin on cytokine and osteocalcin expression in bone tissue during experimental acute otitis media2004In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 25, no 6, p. 254-259Article in journal (Refereed)
    Abstract [en]

    There are indications that bone regulatory and immune systems are closely related. Of special interest in this context is the acute otitis media (AOM), which mainly affects immunologically immature patients and, when complicated, involves bone tissue. To explore host responses in bone tissue during Haemophilus influenzae-induced AOM modified by amoxicillin, a rat model and PCR techniques were used. The treatment eradicated the bacteria and induced changes in the expression profile of osteocalcin, a bone formation marker. The maximum levels of osteocalcin transcripts in the treatment group were delayed by about a week. The mRNA levels never reached the same high levels as in the untreated animal group, but the downregulation was slow and entailed higher osteocalcin mRNA levels for a longer time period in the treated animals. The expression of IL-6 and TNF-alpha, two cytokines associated with bone resorption, remained unaffected by the amoxicillin treatment, whereas the downregulation of IL-10, with suppressive effects on bone resorption, was slower than that during the natural course. By comparing the host responses on the molecular level in different tissues during treated and untreated AOM, new approaches to how to minimize the risks of severe AOM complications may evolve.

  • 10.
    Panezai, Jeneen
    et al.
    Altamash Institute of Dental Medicine, Department of Periodontology, Karachi, Pakistan; Karolinska Institutet, Department of Dental Medicine, Division of Oral Diseases, Section of Periodontology, Huddinge, Sweden; Balochistan University of Information Technology, Engineering and Management Sciences, Department of Microbiology, Faculty of Life Sciences and Informatics, Quetta, Pakistan.
    Ali, Azra
    Habib Medical Centre, Rheumatology Clinic, Karachi, Pakistan, Karachi, Pakistan.
    Ghaffar, Ambereen
    Habib Medical Centre, Rheumatology Clinic, Karachi, Pakistan, Karachi, Pakistan.
    Benchimol, Daniel
    Karolinska Institutet, Department of Dental Medicine, Division of Oral Diagnostics and Rehabilitation, Section of Oral Diagnostics and Surgery, Huddinge, Sweden.
    Altamash, Mohammad
    Altamash Institute of Dental Medicine, Department of Periodontology, Karachi, Pakistan.
    Klinge, Bjӧrn
    Karolinska Institutet, Department of Dental Medicine, Division of Oral Diseases, Section of Periodontology, Huddinge, Sweden; Malmö University.
    Engström, Per-Erik
    Karolinska Institutet, Department of Dental Medicine, Division of Oral Diseases, Section of Periodontology, Huddinge, Sweden.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Upregulation of circulating inflammatory biomarkers under the influence of periodontal disease in rheumatoid arthritis patients2020In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 131, article id 155117Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Periodontal disease (PD) and rheumatoid arthritis (RA) are chronic immuno-inflammatory conditions with osteolysis being a hallmark feature. The influence of PD on RA's systemic inflammatory status and disease activity remains unclear. The objective of this study was to assess the systemic inflammation and disease activity of RA under the influence of PD.

    METHODS: In this case-control study, 38 RA patients (19 with PD and 19 without PD) were compared to 38 non-RA patients and 12 healthy controls. Periodontal parameters (bleeding on probing (BOP), probing pocket depth (PPD), PPD Total, PPD Disease and marginal bone loss (MBL) were determined. Serological analyses included quantification of 92 inflammatory biomarkers using a multiplex proximity extension assay, anti-citrullinated protein antibodies (ACPA), rheumatoid factor (IgM-RF) and erythrocyte sedimentation rate (ESR). RA disease activity was determined using Disease Activity Score for 28 joints (DAS28). All RA patients were on medication.

    RESULTS: IgM-RF was higher in RA patients with PD. PD conditions were more severe in the non-RA group. Inflammatory biomarkers (IL-10RB, IL-18, CSF-1, NT-3, TRAIL, PD-L1, LIF-R, SLAMF1, FGF-19, TRANCE, CST5, STAMPB, SIRT2, TWEAK, CX3CL1, CXCL5, MCP-1) were significantly higher in RA patients with PD than RA without PD. DAS28 associated with twice as many inflammatory biomarkers in RA patients with PD whereas IgM-RF and ACPA associated more frequently with biomarkers in the RA without PD group. IgM-RF correlated inversely with BOP.

    CONCLUSION: Periodontal disease augments systemic inflammation in RA. A profound influence exists independent of autoimmune status.

  • 11.
    Pereira, Maria J.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Azim, Ayesha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hetty, Susanne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Jui Nandi, Bipasha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology. Antaros Medical, Mölndal, Sweden.
    Lundqvist, Martin H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Interleukin-33 inhibits glucose uptake in human adipocytes and its expression in adipose tissue is elevated in insulin resistance and type 2 diabetes2023In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 161, article id 156080Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Interleukin-33 (IL-33) is associated with obesity-related inflammation. We aim to investigate IL-33 expression in subcutaneous adipose tissue (SAT) in type 2 diabetes (T2D) subjects and its effects on human adipocyte glucose uptake.

    METHODS: Expression of IL-33 was analysed in SAT from cohort studies including subjects with and without obesity and T2D and correlated with insulin resistance and obesity markers. Magnetic resonance imaging (MRI) of tissue fat volumes was performed. We investigated the effects of IL-33 treatment on ex vivo adipocyte glucose uptake.

    RESULTS: T2D subjects had higher IL-33 gene and protein expression in SAT than the control subjects. IL-33 mRNA expression was positively correlated with markers of dysglycemia (e.g. HbA1c), insulin resistance (e.g. HOMA-IR) and adiposity (BMI, visceral adipose tissue volume, liver and pancreas fat %). In multiple linear regression analyses, insulin resistance and T2D status were the strongest predictors of IL-33, independent of BMI. IL-33 mRNA expression was negatively correlated with expression of genes regulating adipocyte glucose uptake, lipid storage, and adipogenesis (e.g.glucose transporter 1 and 4 (GLUT1/4), fatty acid binding protein 4 (FABP4), and PPARG). Additionally, incubation of SAT with IL-33 reduced adipocyte glucose uptake and GLUT4 gene and protein expression.

    CONCLUSIONS: Our findings suggest that T2D subjects have higher IL-33 gene and protein expressionin SATthan control subjects, which is associated with insulin resistance and reduced gene expression of lipid storage and adipogenesis markers. IL-33 may reduce adipocyte glucose uptake. This opens up a potential pharmacological route for reversing insulin resistance in T2D and prediabetes.

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  • 12.
    Rydgren, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Öster, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sandberg, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sandler, Stellan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Administration of IL-1 Trap prolongs survival of transplanted pancreatic islets to type 1 diabetic NOD mice2013In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 63, no 2, p. 123-129Article in journal (Refereed)
    Abstract [en]

    We previously reported that IL-1 Trap (a hybrid molecule consisting of the extracellular domain of IL-1 receptor accessory protein and IL-1 receptor type 1 arranged inline and fused to the Fc-portion of IgG1) can protect rat pancreatic islets in vitro against noxious effects induced by IL-1 beta. In this study we tested the effect of administration of a murine IL-1 Trap on the recurrence of disease (ROD) model in non-obese diabetic (NOD) mice. Spontaneously diabetic female NOD mice received implantation of a curative number (600) of syngeneic pancreatic islets beneath their left kidney capsule from young healthy NOD mouse donors. Once a day, the mice were injected subcutaneously with IL-1 Trap (30 mg/kg bodyweight), or an equimolar dose Fc-control protein (8.4 mg/kg bodyweight) or saline. The treatments were maintained until ROD (i.e. a blood glucose value >= 11.1 mM for 2 consecutive days) or until 5 days after transplantation. 3 out of 11 mice treated with IL-1 Trap showed a significantly increased graft survival compared to all other mice, and analysis of relative cytokine mRNA levels in isolated spleen cells showed elevated IL-4 mRNA levels, but no differences in FoxP3 or iNOS staining of grafts, from mice treated with IL-1 Trap, at both endpoints, compared to both control groups. Administration of IL-1 Trap counteracts islet cell destruction in the NOD mouse model of type 1 diabetes. In part this could be due to a shift towards Th2 cytokine production seen in IL-1 Trap treated animals. 

  • 13.
    Sancho Ferrando, Elena
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory. Intensive Care Medicine. Hospital Universitario y Politécnico La Fe. Valencia, Spain..
    Hanslin, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology, Integrative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Frithiof, Robert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Soluble TNF receptors predict acute kidney injury and mortality in critically ill COVID-19 patients: A prospective observational study2021In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 149, article id 155727Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although pneumonia is the hallmark of coronavirus disease 2019 (COVID-19), multiple organ failure may develop in severe disease. TNFα receptors in their soluble form (sTNFR) are involved in the immune cascade in other systemic inflammatory processes such as septic shock, and could mediate the inflammatory activation of distant organs. The aim of this study is to analyse plasma levels of sTNFR 1 and 2 in association with organ failure and outcome in critically ill patients with COVID-19.

    METHODS: After informed consent, we included 122 adult patients with PCR-confirmed COVID-19 at ICU admission. Demographic data, illness severity scores, organ failure and survival at 30 days were collected. Plasma sTNFR 1 and 2 levels were quantified during the first days after ICU admission. Twenty-five healthy blood donors were used as control group.

    RESULTS: Levels of sTNFR were higher in severe COVID-19 patients compared to controls (p < 0.001). Plasma levels of sTNFR were associated to illness severity scores (SAPS 3 and SOFA), inflammation biomarkers such as IL-6, ferritin and PCT as well as development of AKI during ICU stay. sTNFR 1 higher than 2.29 ng/mL and? sTNFR 2 higher than 11.7 ng/mL were identified as optimal cut-offs to discriminate survivors and non-survivors 30 days after ICU admission and had an area under the curve in receiver operating characteristic curve of 0.75 and 0.67 respectively.

    CONCLUSION: Plasma levels of sTNFR 1 and 2 were higher in COVID-19 patients compared to controls and were strongly associated with other inflammatory biomarkers, severity of illness and acute kidney injury development during ICU stay. In addition, sTNFR 1 was an independent predictor of 30-day mortality after adjustment for age and respiratory failure.

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  • 14.
    Siart, Benjamin
    et al.
    a. Department of Anthropology, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria; b. Department of Behavioural Biology, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
    de Oliveira, Felipe
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Shen, Qiujin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Björkesten, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Pekar, Thomas
    d. Department of Biomedical Science, University of Applied Sciences Wiener Neustadt, Johannes Gutenbergstrasse 3, 2700 Wiener Neustadt, Austria.
    Nimmerichter, Alfred
    e. Faculty of Training and Sports Sciences, University of Applied Sciences Wiener Neustadt, Johannes Gutenbergstrasse 3, 2700 Wiener Neustadt, Austria.
    Steinborn, Ralf
    f. Genomics Core Facility,VetCore, University of Veterinary Medicine, Veterinärplatz 1, 1210 Vienna, Austria.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Wallner, Bernard
    b. Department of Behavioural Biology, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria.
    Measurements ofinflammation protein biomarkers in venous plasma, earlobe capillary plasma andin capillary plasma stored on filter paper2017In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023Article in journal (Other academic)
    Abstract [en]

    Multiplex panels for protein biomarkers are increasingly used to analyze blood samples in various fields of clinical research. However, they are rarely used in studies performed outside of a clinical setting. This may in part be due to the relative invasiveness of drawing blood from the vein and because of problems associated with the separation and transport of plasma. Samples collected from the earlobe would be less invasive and could be collected more conveniently. Transportation and storage of such samples could be made easier by blotting plasma on filter paper as dried plasma spots (DPS). The objective of this study was to compare values of multiple protein biomarkers for inflammation measured from three different sources (1) venous plasma, (2) plasma derived from capillary blood from the earlobe and (3) from capillary plasma stored as DPS. Samples from twelve male individuals were assessed with a panel of 92 inflammation related proteins using multiplex proximity extension assay technology. Correlations between the three sample types varied greatly between analytes. In general, a high correlation was observed between capillary plasma and DPS, with 33 analytes showing a correlation value of ρ > 0.8 in the two sample types. At this level of correlation (ρ > 0.8) 14 analytes correlated between venous and capillary plasma in contrast to only six analytes in the comparison of venous blood with DPS. We conclude that collecting samples from the earlobe is a feasible and less invasive alternative to venipuncture, but that the comparability with measures obtained from venous samples varies greatly between proteins.

  • 15. Sjöholm, Kajsa
    et al.
    Lundgren, Magdalena
    Olsson, Maja
    Eriksson, Jan W
    Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy, Göteborg University, Göteborg, Sweden.
    Association of serum amyloid A levels with adipocyte size and serum levels of adipokines: differences between men and women2009In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 48, no 3, p. 260-266Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to characterize the association between adipocyte enlargement and circulating levels of serum amyloid A (SAA). Furthermore, we wanted to search for possible associations with measures of glycemic control and levels of circulating adipokines and/or inflammatory markers in men and women with a large range in body mass index. The study cohort consisted of 167 subjects, 114 non-diabetic and 53 with Type 2 diabetes. Adipocyte diameter as well as circulating levels of SAA, C-reactive protein (CRP), adiponectin, leptin, interleukin-6, tumor necrosis factor alpha, glucose and insulin were measured. Women had higher serum levels of SAA than men (p=0.044). SAA levels were weakly but positively correlated with BMI (p=0.043) and % body fat (p=0.027) in all subjects as well as subcutaneous adipocyte diameter (p=0.034) in women. Furthermore, in all subjects we found correlations between SAA levels and levels of CRP (p<0.001), interleukin-6 (p<0.001), leptin (p=0.003), insulin (p=0.006), HbA1c (p=0.02) and HOMA-IR (p=0.002). A majority of the correlations were strongest in women. In conclusion, serum levels of SAA are strongly correlated with serum levels of inflammatory markers as well as measures of glycemic control. There seems to be large sex differences in these associations suggesting that sex-specific factors need to be considered when analyzing SAA levels in relation to metabolic disease.

  • 16. Tamm, Katia Pokrovskaja
    et al.
    Kolosenko, Iryna
    Fryknäs, Mårten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Johnsson, Per
    Forsberg, Sofi
    Brnjic, Slavica
    Rassoolzadeh, Hanif
    Pellegrini, Paola
    Grander, Dan
    Larsson, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Linder, Stig
    De Milito, Angelo
    Association of interferon stimulated genes and IRF9 upregulation with drug resistance in multicellular spheroids and monolayer cells upon crowding2013In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 63, no 3, p. 303-303Article in journal (Other academic)
  • 17.
    Thorvaldson, Lina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Stålhammar, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sandler, Stellan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Effects of a diabetes-like environment in vitro on cytokine production by mouse splenocytes2008In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 43, no 1, p. 93-97Article in journal (Refereed)
    Abstract [en]

    Elevated levels of glucose and free fatty acids as well as changes in the cytokine production are common features of both type 1 and type 2 diabetes. Especially regarding type 1 diabetes, immunological factors are believed to be responsible for much of the disease pathology. The aim of this study was to investigate whether the diabetic environment in itself could affect cytokine production. Spleen cells from normal mice were cultured for 96 h with addition of different concentrations of glucose (2.8, 5.6, 11.1, 28 mM) or the free fatty acid palmitate (50-100 microM). Cytokine supernatant secretions and mRNA expressions were determined. The cytokine production was highest in cells cultured at 11.1mM glucose. TNFalpha and IFNgamma secretion was decreased by high glucose. Palmitate and/or the ethanol used to dissolve it had a suppressive effect on the secretion of all the investigated cytokines. This effect was counteracted by an elevated glucose concentration for TNFalpha and IFNgamma, but not IL-10. In conclusion, our data suggest that metabolic aberrations characterizing a diabetic environment can have a direct impact on cytokine production by immune cells.

  • 18. Velasquez, Ilais Moreno
    et al.
    Kumar, Jitender
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bjorkbacka, Harry
    Nilsson, Jan
    Silveira, Angela
    Leander, Karin
    Berglund, Anita
    Strawbridge, Rona J.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Melander, Olle
    Almgren, Peter
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hamsten, Anders
    de Faire, Ulf
    Gigante, Bruna
    Duffy antigen receptor genetic variant and the association with Interleukin 8 levels2015In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 72, no 2, p. 178-184Article in journal (Refereed)
    Abstract [en]

    The aim of this study is to identify loci associated with circulating levels of Interleukin 8 (IL8). We investigated the associations of 121,445 single nucleotide polymorphisms (SNPs) from the Illumina 200K CardioMetabochip with IL8 levels in 1077 controls from the Stockholm Heart Epidemiology Program (SHEEP) study, using linear regression under an additive model of inheritance. Five SNPs (rs12075A/G, rs13179413C/T, rs6907989T/A, rs9352745A/C, rs1779553T/C) reached the predefined threshold of genome-wide significance (p < 1.0 x 10(-5)) and were tested for in silico replication in three independent populations, derived from the PIVUS, MDC-CC and SCARF studies. IL8 was measured in serum (SHEEP, PIVUS) and plasma (MDC-CC, SCARF). The strongest association was found with the SNP rs12075 A/G, Asp42Gly (p = 1.6 x 10(-6)), mapping to the Duffy antigen receptor for chemokines (DARC) gene on chromosome 1. The minor allele G was associated with 15.6% and 10.4% reduction in serum IL8 per copy of the allele in SHEEP and PIVUS studies respectively. No association was observed between rs12075 and plasma IL8. Conclusion: rs12075 was associated with serum levels but not with plasma levels of IL8. It is likely that serum IL8 represents the combination of levels of circulating plasma IL8 and additional chemokine liberated from the erythrocyte DARC reservoir due to clotting. These findings highlight the importance of understanding ILS as a biomarker in cardiometabolic diseases. 

  • 19.
    Wohlin, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Vessby, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Both cyclooxygenase- and cytokine-mediated inflammation are associated with carotid intima-media thickness2007In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 38, no 3, p. 130-136Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Common carotid artery intima-media thickness (CCA-IMT) is a valid index of atherosclerosis, which is viewed as an inflammatory disease. It is unknown if various modes of inflammation (cyclooxygenase [COX]-mediated, cytokine-mediated), oxidative stress and anti-oxidants are independently related to CCA-IMT. METHODS AND RESULTS: We investigated cross-sectional relations between CCA-IMT measured by B-mode ultrasound and COX-mediated inflammation (as measured by 15-keto-dihydro-prostaglandin F(2alpha) [PGF(2alpha)], cytokine-mediated inflammation (interleukin-6 [IL-6], high sensitivity C-reactive protein [hsCRP] and serum amyloid A protein [SAA]), oxidative stress (8-iso-PGF(2alpha), an F(2)-isoprostane; a non-enzymatic, free radical-induced product of arachidonic acid), and tocopherols (anti-oxidants) in a small subset of a population-based sample of elderly men (n=234) stating no use of anti-inflammatory medications. In a backward-stepwise regression analysis of correlates of CCA-IMT (with PGF(2alpha), hsCRP, IL-6, SAA, F(2)-isoprostanes, tocopherols, diabetes, body mass index (BMI), beta-blocker, statin treatment, smoking, hypertension and cholesterol), PGF(2alpha), CRP, beta-blocker treatment, diabetes and BMI were independently associated with CCA-IMT. There were no associations between F(2)-isoprostanes or tocopherols and CCA-IMT in this study. CONCLUSION: This study suggests both COX- and cytokine-mediated inflammation to be independently associated with increased CCA-IMT, implying that there might be more than one mode of inflammation involved in atherogenesis.

  • 20.
    Woschnagg, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Garcia, Rodolfo C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The effect of IL-5 treatment on the stimulation-induced phosphorylation of proteins in blood eosinophils2004In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 28, no 3, p. 137-148Article in journal (Refereed)
    Abstract [en]

    Eosinophils are selectively primed and activated by the cytokine IL-5. The aim of this investigation was to study the effects of IL-5 treatment on stimulation-dependent protein phosphorylations, in human peripheral blood eosinophils. After IL-5 treatment, basal phosphorylation patterns showed increases in the phosphorylation of 67, 80 and 93 kDa proteins. Cell stimulations resulted in the following protein phosphorylation increases: 50, 60, 67, 80 and 93 kDa (PMA); 50, 67, 80 and 93 kDa (STZ); and 67, 80 and 93 kDa (IL-5). The phosphorylation of the 50 and 60 kDa proteins was shown to be MEK-independent and dependent on some PKC isoform/s, whereas that of the 67, 80 and 93 kDa proteins was both MEK- and PKC-alpha, beta, delta, gamma, tau and zeta-independent. A phosphoprotein of 50 kDa was identified as p47(phox) and another of 67 kDa protein as the tyrosine phosphatase SHPTP-1. Incubation with IL-5 followed by cell stimulation increased the total phosphorylation of p47(phox). Bidimensional (IEF-SDS/PAGE) analysis showed that the combination of IL-5 treatment followed by stimulation with either PMA or STZ induced the formation of an additional, hyperphosphorylated form of p47(phox). The presence of this form would explain the higher NADPH oxidase activity normally observed after IL-5 priming.

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