loxoribine and Multiple-Sclerosis--Relapsing-Remitting

We report that B cells from patients with RRMS have decreased endogenous IFN-β secretion and deficient IFN receptor (IFNAR)1/2 and TLR7 gene expression in comparison to healthy controls (HCs), which may contribute to disregulation of cytokine secretion by B cells. We propose that TLR7 and TLR9 stimulation with loxorubin (LOX) and CpG, in combination with exogenous IFN-β may effectively reconstitute endogenous IFN-β production deficit and induce the secretion of immunoregulatory cytokines by B cells. Both LOX/IFN-β and CpG/IFN-β in-vitro treatments of B cells from RRMS patients induced higher endogenous IFN-β gene expression in comparison to the exogenous IFN-β alone. CpG/IFN-β combination induced higher secretion of IL-10, TGF-β, and IL-27 in comparison to stimulation with IFN-β. Our study provides a basis for future clinical studies employing IFN-β and TLR7/9 agonists, which may enhance the resolution of the inflammatory response in RRMS.

Topics: B-Lymphocytes; Case-Control Studies; CD4 Antigens; Cytokines; Drug Synergism; Female; Glatiramer Acetate; Guanosine; Humans; Immunologic Factors; Interferon Regulatory Factor-7; Interferon-beta; Male; Methylprednisolone; Multiple Sclerosis, Relapsing-Remitting; Myeloid Differentiation Factor 88; STAT1 Transcription Factor; Tetraspanin 29; Toll-Like Receptor 7; Toll-Like Receptor 9