Decreased interferon-α production in response to CpG DNA dysregulates cytokine responses in patients with multiple sclerosis

Type I interferons (IFNs), represented by IFN-alpha and beta, activate immune effector cells belonging to the innate and adaptive immune systems. Plasmacytoid dendritic cells (pDCs) produce IFN-alpha in response to CpG DNA. We aimed to examine the impact of pDC-produced IFN-alpha on the adaptive immune system in Multiple Sclerosis (MS). Our results demonstrated that CpG DNA-induced IFN-alpha production was significantly decreased in PBMCs from MS patients. Decreased levels of IL-12 p70, IFN-gamma, and IL-17 and increased level of IL-10 were found in CpG DNA-treated PBMCs of healthy subjects unlike in those from MS patients. In samples pre-treated with IFN-alpha and IFN-beta, decreased levels of IL-12 p70, IFN-gamma, and IL-17 and increased level of IL-10 were detected in PBMCs from MS patients. These results suggest that CpG DNA-induced decreased IEN-alpha production causes pro-inflammatory cytokine secretion, and either IFN-alpha or IFN-beta induces anti-inflammatory cytokine secretion in the adaptive immune system in MS. (C) 2012 Elsevier Inc. All rights reserved.