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Title: Prevention of primary non-function of islet xenografts in autoimmune diabetic NOD mice by anti-inflammatory agents
Authors: Gysemans, Conny
Stoffels, Katinka
Giulietti, Annapaula
Overbergh, Lutgart
Waer, Mark
Lannoo, Matthias
Feige, Ulrich
Mathieu, Chantal # ×
Issue Date: Aug-2003
Series Title: Diabetologia vol:46 issue:8 pages:1115-23
Abstract: AIMS/HYPOTHESIS. High levels of inflammation locally in the graft during the initial days after transplantation can cause primary non-function (PNF) of grafted xenogeneic islets in NOD mice. The aim of this study was to explore in a model of spontaneous diabetes, the NOD mouse, the potential of anti-inflammatory agents in the prevention of PNF after xenogeneic islet transplantation. METHODS. Spontaneously diabetic NOD mice were transplanted with 300 rat islets. Animals were treated with acetylsalicylic acid (AsA), rofecoxib, TGF-beta or IL-1 receptor antagonist (IL-1ra). Intra-graft expression of inflammation-related molecules was measured by real time PCR 8 h post-transplantation. At the same time point, plasma nitrite levels were measured. RESULTS. Xenogeneic islets transplanted in control spontaneously diabetic mice resulted in PNF in 16 out of 38 mice (42%). Initial graft loss was not altered by administration of rofecoxib (30%) or TGF-beta (25%). AsA reduced the rate of rapid graft loss to 8% ( p<0.05 vs controls) and administration of IL-1ra even totally prevented PNF (0%, p<0.05 vs controls). Furthermore, all therapies prolonged the mean survival time of xenogeneic islet grafts. The inhibition of PNF by AsA was associated with decreased intra-islet levels of inflammation-related molecules (IL-1, TNF-alpha, iNOS, COX-2) and chemokines (MCP-1 and MIP-3alpha). Finally, also a diminished production of systemic nitrite levels was observed in AsA- and IL-1ra-treated islet recipients. CONCLUSIONS/INTERPRETATION. These data show that treatment with AsA or IL-1ra prevents PNF after islet transplantation in spontaneously diabetic NOD mice. Moreover, the involvement of non-specific inflammation is recognized in xenogeneic islet PNF in spontaneously diabetic NOD mice.
ISSN: 0012-186X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical and Experimental Endocrinology
Laboratory of Nephrology
Clinical Residents Medicine
Research Group Experimental Neurology
Laboratory of Experimental Transplantation
× corresponding author
# (joint) last author

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