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Administration of IL-1 Trap prolongs survival of transplanted pancreatic islets to type 1 diabetic NOD mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
2013 (English)In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 63, no 2, 123-129 p.Article in journal (Refereed) Published
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. 

Place, publisher, year, edition, pages
2013. Vol. 63, no 2, 123-129 p.
Keyword [en]
Type 1 diabetes, Non-obese diabetic mice, Interleukin-1 Trap, Recurrence of disease model, Interleukin-4
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-204833DOI: 10.1016/j.cyto.2013.04.020ISI: 000321088100007OAI: oai:DiVA.org:uu-204833DiVA: diva2:640335
Available from: 2013-08-13 Created: 2013-08-12 Last updated: 2017-12-06Bibliographically approved

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Rydgren, TobiasÖster, ElinSandberg, MonicaSandler, Stellan

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