uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Influence of cyclooxygenase inhibitors on gut immune cell distribution and apoptosis rate in experimental sepsis
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences.
Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-92555OAI: oai:DiVA.org:uu-92555DiVA: diva2:165681
Available from: 2005-02-17 Created: 2005-02-17 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Inflammatory Reactions in Peritonitis and Malignant Obstructive Jaundice: Clinical and Experimental Studies with Special Emphasis on the Cellular Immune Response
Open this publication in new window or tab >>Inflammatory Reactions in Peritonitis and Malignant Obstructive Jaundice: Clinical and Experimental Studies with Special Emphasis on the Cellular Immune Response
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Patients with peritonitis or malignant obstructive jaundice (HPB+) have an increased morbidity and mortality due to sepsis. An altered cell-mediated immunity in the intestinal mucosa might promote gut barrier failure, increased endotoxin and cytokine release and bacterial translocation (BT) in these conditions. A clinically relevant rat model of polymicrobial peritonitis induced sepsis by cecal ligation and puncture (CLP) was used. Septic animals demonstrated a superficial injury in the small intestinal mucosa, and a significant reduction in T lymphocytes in the villi, as well as increased number of macrophages in the villi and in the MLNs as compared to sham. CLP caused increased concentration of TNF-α and IL-6 in ascitic fluid. CLP + the immunomodulator Linomide decreased the TNF-α level, reduced mucosal damage and attenuated the changes in T lymphocytes and macrophages observed following CLP. CLP + selective cyclooxygenase (COX)-2 inhibitor (SC-236) or nonselective COX inhibitor (indometacin) decreased the amount of macrophages in the mucosa and the MLNs compared to untreated CLP. CLP + indometacin decreased T lymphocytes in the villi and MLNs. SC-236 + CLP reduced mucosal injury and cytokine release as compared to indometacin. An increased rate of apoptosis in both the mucosa and MLNs was seen following CLP; COX inhibitors enhanced this phenomenon in the MLNs.

BT occurred infrequently in patients with acute peritonitis and in HPB+ there was no evidence of BT. Peritonitis and HPB+ causes significant inflammatory cellular reactions as increased endotoxin and cytokine plasma levels and an altered immune cell distribution in MLNs, in HPB+ a high rate of apoptosis in MLNs was observed.

An altered pattern of immunocompetent cells within the mucosa and in MLNs was found in experimental and clinical peritonitis as in HPB+. Lymphocyte depletion may be a result of increased apoptosis, which could reduce the ability of septic or jaundice patients to eradicate infection.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 65 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 3
Surgery, CLP, sepsis, peritonitis, bacterial translocation, malignant obstructive jaundice, Linomide, COX inhibitor, SC-236, indometacin, T lymphocyte, macrophage, mucosa, MLN, gut immune cell distribution, mucosal injury, cytokines, TNF-α, IL-6, IL-10, endotoxin, caspase-3, apoptosis, Kirurgi
National Category
urn:nbn:se:uu:diva-4767 (URN)91-554-6138-7 (ISBN)
Public defence
2005-03-11, Auditorium Minor, Gustavianum, Akademigatan 3, Uppsala, 09:15
Available from: 2005-02-17 Created: 2005-02-17Bibliographically approved

Open Access in DiVA

No full text

By organisation
Department of Surgical Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 138 hits
ReferencesLink to record
Permanent link

Direct link