Interleukin-1 antagonists and other cytokine blockade strategies for type 1 diabetes.

ABSTRACT: Proinflammatory cytokines stimulate adaptive immunity and attenuate T cell regulation and tolerance induction. They also profoundly impair β-cell function, proliferation, and viability, activities of similar importance in the context of type 1 diabetes (T1D). Detailed knowledge of the molecular mechanisms of β-cell toxicity has been gathered within the last 2-3 decades. However, the efficacy of individual proinflammatory cytokine blockade in animal models of T1D has been inconsistent and generally modest, except in the context of islet transplantation. This suggests that the timing of the cytokine blockade relative to anti-β-cell immune activation is critical, and that combination therapy may be required. In randomized, placebo-controlled, clinical trials of limited power, TNF-α (but not I

SUBMITTER: Mandrup-Poulsen T 

PROVIDER: S-EPMC3740701 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature