New members of the interleukin-12 family of cytokines: IL-23 and IL-27 modulate autoimmune diabetes.
Multiple low doses of streptozotocin (5 x 40 mg/kg) given to susceptible male C57BL6 mice induced delayed and sustained hyperglycemia accompanied by body weight loss, mononuclear cell infiltration in the islet, and apoptosis of beta cells. Shorter regimes (4 x 40 mg/kg) did not have such effect. Administration of IL-23 at a dose of 400 ng/mL for 10 consecutive days concomitantly with this subdiabetogenic regimen of STZ, however, induced significant hyperglycemia, weight loss, and mononuclear cellular infiltration. The same regimen of IL-27 induced milder effect on glycemia and no weight loss inspite of a massive peri-islet and intra-islet infiltration of mononuclear cells. The molecular mechanisms underlying the actions of these cytokines on diabetogenesis is under study.
Mensah-Brown
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EP
Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates.
Shahin
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A
Al-Shamsi
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Lukic
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ML
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology* / Q000628:therapy*; D001835:Body Weight / Q000187:drug effects; D016207:Cytokines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006651:Histocytochemistry; D006943:Hyperglycemia / Q000139:chemically induced / Q000188:drug therapy; D007150:Immunohistochemistry; D053759:Interleukin-23 / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D007378:Interleukins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D013311:Streptozocin / Q000008:administration & dosage / Q000633:toxicity; D013997:Time Factors
D016207:Cytokines; C486767:Il27 protein, mouse; D053759:Interleukin-23; D007378:Interleukins; D011994:Recombinant Proteins; D013311:Streptozocin