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

OBJECTIVE

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.

RESEARCH DESIGN

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.

RESULTS

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.

CONCLUSIONS

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.