[Interleukin 1 receptor antagonists prevent the induction of experimental insulin-dependent autoimmune diabetes].
During the induction of diabetes with multiple low-dose of streptozotocin (40-45 mg/kg body weigh for 5 consecutive days) starting from day 3, CBA mice were injected repeatedly (10 daily injections) with either rat IL-1 inhibitor (IL-1 INH) derived from glucocorticoid-treated macrophages, or with recombinant DNA produced human IL-1 receptor antagonist (rIL-1ra). Althow not showing identity with each other, both agents by neutralisation of the activity of endogenous IL-1 interfered with the induction of diabetes. While control streptozotocin-treated mice developed sustained hyperglicemia with the late onset, histologically characterized with insulitis and islet cell destruction, mice injected with rat IL-1 INH, either in a form of dialyzed crude macrophage supernatant or partialy enriched 50-100 kDa fraction, remained normoglycemic. In agreement with diabetic status, insulitis and islet cell destruction were not observed in IL-1 INH treated mice. Human IL-1ra had milder, althow also significant protective effect. Our results, thus, suggest that IL-1 mediated immunopathogenic and/or inflammatory processes which lead to insulin-dependent diabetes, may be modulated by specific in vivo blockade of IL-1 receptors.
Stosić-Grujicić
S
S
Lukić
M
M
Ostajić
N
N
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA
D001786:Blood Glucose; D053590:Interleukin 1 Receptor Antagonist Protein