title: Salicylate prevents virus-induced type 1 diabetes in the BBDR rat.
abstract: Epidemiologic and clinical evidence suggests that virus infection plays an important role in human type 1 diabetes pathogenesis. We used the virus-inducible BioBreeding Diabetes Resistant (BBDR) rat to investigate the ability of sodium salicylate, a non-steroidal anti-inflammatory drug (NSAID), to modulate development of type 1 diabetes. BBDR rats treated with Kilham rat virus (KRV) and polyinosinic:polycytidylic acid (pIC, a TLR3 agonist) develop diabetes at nearly 100% incidence by ~2 weeks. We found distinct temporal profiles of the proinflammatory serum cytokines, IL-1β, IL-6, IFN-γ, IL-12, and haptoglobin (an acute phase protein) in KRV+pIC treated rats. Significant elevations of IL-1β and IL-12, coupled with sustained elevations of haptoglobin, were specific to KRV+pIC and not found in rats co-treated with pIC and H1, a non-diabetogenic virus. Salicylate administered concurrently with KRV+pIC inhibited the elevations in IL-1β, IL-6, IFN-γ and haptoglobin almost completely, and reduced IL-12 levels significantly. Salicylate prevented diabetes in a dose-dependent manner, and diabetes-free animals had no evidence of insulitis. Our data support an important role for innate immunity in virus-induced type 1 diabetes pathogenesis. The ability of salicylate to prevent diabetes in this robust animal model demonstrates its potential use to prevent or attenuate human autoimmune diabetes.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
authors.forename: Chaoxing
authors.initials: C
authors.lastname: Yang
authors.forename: Agata
authors.initials: A
authors.lastname: Jurczyk
authors.forename: Philip
authors.initials: P
authors.lastname: diIorio
authors.forename: Elaine
authors.initials: E
authors.lastname: Norowski
authors.forename: Michael A
authors.initials: MA
authors.lastname: Brehm
authors.forename: Christian W
authors.initials: CW
authors.lastname: Grant
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Guberski
authors.forename: Dale L
authors.initials: DL
authors.lastname: Greiner
authors.forename: Rita
authors.initials: R
authors.lastname: Bortell
mesh_terms: D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000188:drug therapy* / Q000821:virology*; D005260:Female; D008297:Male; D017992:Parvovirus / Q000472:pathogenicity; D011070:Poly I-C / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000627:therapeutic use*
chemical_list: D012459:Salicylates; D011070:Poly I-C