Toll-like receptors, the NLRP3 inflammasome, and interleukin-1β in the development and progression of type 1 diabetes

Traditionally, type 1 diabetes (T1D) has been thought of as a disease of cellular immunity, but there is increasing evidence that components of the innate immune system, controlled largely by Toll-like receptors (TLRs), play a significant role in T1D development. TLRs are pattern-recognition molecules on immune cells that recognize pathogens, leading to the production of cytokines such as interleukin-1 beta (IL1 beta, encoded by the IL1B gene). IL1 beta is increased in patients with newly diagnosed T1D and likely acts as an early inflammatory signal in T1D development. Because hyperglycemia is a hallmark of T1D, the effects of hyperglycemia on IL1 beta expression in peripheral blood mononuclear cells (PBMCs) and islet cells have been examined, but with inconsistent results, and the mechanisms leading to this increase remain unknown. Fatty acids stimulate IL1 beta expression and may promote inflammation, causing hyperglycemia and insulin resistance. The mechanisms by which IL1 beta is involved in T1D pathogenesis are controversial. Overall, studies in pancreatic beta-cells suggest that IL1 beta-mediated damage to islet cells involves multiple downstream targets. Potential therapies to decrease the progression of T1D based on IL1 beta biology include pioglitazone, glyburide, IL1 receptor antagonists, and agents that remove IL1 beta from the circulation.