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

Sanda, S., Bollyky, J., Standifer, N., Nepom, G., Hamerman, J.A., Greenbaum, C.

Journal Clin Immunol. Year 2010
Species Human Volume
CRP, IFN-γ, IL-1β, IL-10, IL-12 p70, IL-17, IL-2, IL-4, IL-5, IL-6, IL-8, MCP-1, MIP-1α, TNF-α Page #
Matrix Tested Serum Cytokines & Chemokines

Abstract

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.

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