Program in Molecular Medicine
Endocrine System Diseases | Immunity | Immunopathology | Nutritional and Metabolic Diseases
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-1beta, IL-6, IFN-gamma, IL-12, and haptoglobin (an acute phase protein) in KRV+pIC treated rats. Significant elevations of IL-1beta 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-1beta, IL-6, IFN-gamma 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.
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Copyright 2013 Yang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
Yang C, Jurczyk A, diIorio P, Norowski E, Brehm MA, et al. (2013) Salicylate Prevents Virus-Induced Type 1 Diabetes in the BBDR Rat. PLoS ONE 8(10): e78050. doi:10.1371/journal.pone.0078050. Link to article on publisher's site
Yang, Chaoxing; Jurczyk, Agata; diIorio, Philip J.; Norowski, Elaine; Brehm, Michael A.; Grant, Christian W.; Guberski, Dennis L.; Greiner, Dale L.; and Bortell, Rita, "Salicylate prevents virus-induced type 1 diabetes in the BBDR rat" (2013). Open Access Articles. 2405.