IFN-alpha induces IL-10 production and tilt the balance between Th1 and Th17 in Behcet disease.

BACKGROUND AND AIMS: Interferon alpha (IFN-alpha) is an effective treatment for patients with active Behcet disease (BD). Besides its antiviral property, IFN-alpha is a cytokine with pleiotropic effects that can generate an anti-inflammatory environment or inhibit specific inflammatory T cells such as Th1 and Th17 cells. However, it is not known, in BD patients, whether IFN-alpha inhibits pro inflammatory T cells, or induces anti-inflammatory properties in T cells. METHODS: Total memory CD45RO(+) T cells purified from peripheral blood mononuclear cells (PBMCs) obtained from patients with active BD (N=5), systemic lupus erythematosus (SLE, N=5) or healthy control (HC, N=6) were cultured in vitro with or without IFN-alpha. Levels of IFN-gamma, IL-17, IL-10, IL-6, and TNF-alpha in the supernatants were analyzed by ELISA, Cytometric Beads Array (CBA) or intracellular cytokine staining. We analyzed the production of IL-10 on the memory subsets Th1 (mTh1), Th2 (mTh2) and Th17 (mTh17). RESULTS: IFN-alpha significantly increased IFN-gamma level in memory CD4(+) T cells in BD patients and HC, but not SLE patients. IL17 was not inhibited by IFN-alpha in BD or in SLE patients. However, IFN-alpha modulated the pro- and anti-inflammatory cytokines secreted by T cells as it increased the IL-10/IL-6 ratio in BD and HC, but not SLE patients. We further demonstrated that IFN-alpha increased IL-10 secretion in each memory subset mTh1, mTh2 and mTh17. CONCLUSIONS: In BD, IFN-alpha promotes a regulatory Th1 response through IL-10 secretion. This effect may explain the efficacy of IFN-alpha in inflammatory disease.