[The effect of in vivo blockade of interleukin-1 and interferon-gamma on the autoimmune syndrom in the experimental model of graft versus host disease].
The acute graft versus host disease (GVHD) is induced in sublethaly irradiated (AOxDA)F1 hybrid rats following transfer of parental AO spleen cells. However, when recipients were treated with anti-CD8 mAb on days -4, -2, 0, 4 and 8 in relation to parental cell transfer, acute GVHD converts to a chronic GVHD with an autoimmune phenomena. Diseased animals produce antinuclear antibodies and display glucose intolerance curves that are significantly abnormal. Histological examination of pancreata from diseased animals revealed milde insulitis with concomitant islet destruction. By using this model of anti-CD8 mAb treated animals we have investigated the role of interferon-gamma (IFN-gamma) and interleukin-1 (IL-1) in the complex pathology associated with GVHD. For this purpose, during the first 10 days of GVHD induction, we applied in vivo treatment with either anti-IFN-gamma mAb or with specific inhibitor of IL-1 activity (IL-1 INH). Treatment of F1 recipients with mAb to rat IFN-gamma resulted in an acceleration of glucose intolerance. In contrast to this, treatment of recipients with macrophage-derived IL-1 INH fully normalized their impaired glucose tolerance. Our data suggest that TH1 cells and their cytokine IFN-gamma down-regulate diabetes-like syndrom in chronic GVHD, while either IL-1 alone or IL-1 dependent TH2 cells support these processes. This further indicates the possibility to manipulate chronic GVHD-related immunopathological processes by blocking corresponding cytokines.
Ejedus
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Stosić-Grujicić
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Lukić
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D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018149:Glucose Intolerance; D006086:Graft vs Host Disease / Q000276:immunology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000502:physiology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D007371:Interferon-gamma