title: Interleukin-1 promotes hyperglycemia and insulitis in mice normally resistant to streptozotocin-induced diabetes.
abstract: By administering physiological doses of interleukin-1 (IL-1) concurrently with multiple low doses of the beta cell toxin streptozotocin (MSZ), we observed an augmentation of diabetes by IL-1 in four different strains of mice. Augmentation of hyperglycemia by IL-1 was most prominent in the two MSZ-resistant mouse strains Balb/cJ and A/J. Furthermore, concurrent treatment with IL-1 and MSZ rendered these MSZ-resistant mice susceptible to the development of significant insulitis when compared to mice treated with MSZ alone. Development of insulitis was dependent upon the dose of IL-1; it was only observed at an IL-1 dose of 250 ng/kg body weight. Analysis of the leukocytic infiltrate in the islets of mice after treatment with 250 ng/kg IL-1 plus MSZ revealed the presence of L3T4+ and Lyt-2+ T lymphocytes. Administration of MSZ alone or IL-1 alone did not produce diabetes in the MSZ-resistant mice, indicating that neither of these agents was toxic to the beta cells by itself. We conclude that IL-1 synergizes with MSZ to augment diabetes in mice that are normally resistant to the diabetogenic effects of MSZ.
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75235.
authors.forename: S J
authors.initials: SJ
authors.lastname: Zunino
authors.forename: L F
authors.initials: LF
authors.lastname: Simons
authors.forename: J F
authors.initials: JF
authors.lastname: Sambrook
authors.forename: M J
authors.initials: MJ
authors.lastname: Gething
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced* / Q000276:immunology; D004198:Disease Susceptibility; D004357:Drug Synergism; D006943:Hyperglycemia / Q000209:etiology*; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010195:Pancreatitis / Q000209:etiology* / Q000473:pathology; D013045:Species Specificity; D013311:Streptozocin
chemical_list: D007375:Interleukin-1; D013311:Streptozocin