An interleukin-1 receptor antagonist protein was evaluated with regard to its efficacy in allogeneic and xenogeneic islet transplantation. Alloxan-induced diabetic C57BL/6 (H-2b) mice were transplanted under the kidney capsule with 500 C57BL/Ks (H-2d) mouse islets. Alzet osmotic pumps, which release their content over an 11- to 13-day period, were implanted subcutaneously for continuous infusion of interleukin-1 receptor antagonist protein (1.0, 5.0, 8.0 mg · kg−1 · day−1) or phosphate-buffered saline. Blood glucose determinations were performed every second or third day; at death, the islet-bearing kidneys were morphologically evaluated. Mice treated initially with the higher interleukin-1 receptor antagonist protein concentrations were followed for an additional period after cessation of the drug release to evaluate whether a transitory interleukin-1 receptor antagonist protein treatment would induce tolerance to the graft. All phosphate-buffered saline–treated mice were hyperglycemic 11 days after islet allotransplantation. Most of their grafts were heavily infiltrated with mononuclear cells. In the various interleukin-1 receptor antagonist protein–treated groups, 60–80% of the mice were normoglycemic after 11 days. Moreover, light microscopic examinations showed that most mice treated with interleukin-1 receptor antagonist protein had normal islet grafts or grafts infiltrated with only a few mononuclear cells. After interruption of interleukin-1 receptor antagonist protein infusion (8.0 mg · kg−1 · day−1), all animals developed hyperglycemia within 2–9 days. In xenogeneic experiments, 500–750 fetal porcine islet-like cell clusters were transplanted under the kidney capsule of normoglycemic C57BL/6 mice. These animals were treated either with interleukin-1 receptor antagonist protein (8.0 mg · kg−1 · day−1) or phosphate-buffered saline. Examination of graft morphology on day 11 showed similarly rejected grafts in both groups. In conclusion, these data suggest that interleukin-1 receptor antagonist protein protects islet allograft, but not xenograft, against acute rejection. Interleukin-1 receptor antagonist protein may become useful as an adjuvant immunosuppressive drug after human islet transplantation.
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Original Articles|
December 01 1993
Treatment With an Interleukin-1 Receptor Antagonist Protein Prolongs Mouse Islet Allograft Survival
Jan-Olov Sandberg;
Jan-Olov Sandberg
Department of Medical Cell Biology, Uppsala University
Uppsala, Sweden
Immunological Division, BASF Bioresearch Corporation
Cambridge, Massachusetts
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Decio L Eizirik;
Decio L Eizirik
Department of Medical Cell Biology, Uppsala University
Uppsala, Sweden
Immunological Division, BASF Bioresearch Corporation
Cambridge, Massachusetts
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Stellan Sandler;
Stellan Sandler
Department of Medical Cell Biology, Uppsala University
Uppsala, Sweden
Immunological Division, BASF Bioresearch Corporation
Cambridge, Massachusetts
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Daniel E Tracey;
Daniel E Tracey
Department of Medical Cell Biology, Uppsala University
Uppsala, Sweden
Immunological Division, BASF Bioresearch Corporation
Cambridge, Massachusetts
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Arne Andersson
Arne Andersson
Department of Medical Cell Biology, Uppsala University
Uppsala, Sweden
Immunological Division, BASF Bioresearch Corporation
Cambridge, Massachusetts
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Address correspondence and reprint requests to Dr. Jan-Olov Sandberg, Department of Medical Cell Biology, Biomedical Center, P.O. Box 571, S–751 23 Uppsala, Sweden.
Diabetes 1993;42(12):1845–1851
Article history
Received:
July 14 1992
Revision Received:
July 29 1993
Accepted:
July 29 1993
PubMed:
8243831
Citation
Jan-Olov Sandberg, Decio L Eizirik, Stellan Sandler, Daniel E Tracey, Arne Andersson; Treatment With an Interleukin-1 Receptor Antagonist Protein Prolongs Mouse Islet Allograft Survival. Diabetes 1 December 1993; 42 (12): 1845–1851. https://doi.org/10.2337/diab.42.12.1845
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