Short-term IL-1beta blockade reduces monocyte CD11b integrin expression in an IL-8 dependent fashion in patients with type 1 diabetes.

Interleukin 1-beta (IL-1beta) is a major inflammatory cytokine. Blockade of the IL-1beta pathway is therapeutically efficacious in type 2 diabetes, but the mechanistic effects on the immune system are incompletely understood.We administered an IL-1 receptor antagonist, anakinra, to 7 type 1 diabetes patients in order to investigate the immunologic and metabolic effects of this drug. Mechanistic assays were performed before and after drug administration.A novel signature was observed, with reduced serum interleukin 8 (IL-8) levels and reduced CD11b integrin expression on monocytes associated with increased CXCR1 expression.This set of linked phenotypes suggests that blockade of the IL-1beta pathway results in the reduced ability of mononuclear cells to traffic to sites of inflammation. Mechanistic studies from large scale trials using IL-1 blockade in type 1 diabetes should focus on changes in monocyte trafficking and the IL-8 pathway.