Multiple sclerosis: deficient in vitro responses of blood mononuclear cells to IFN-beta.

Abstract

IFN-beta may modify the clinical course of multiple sclerosis (MS) but is not curative, and there are also patients whose disease does not respond to IFN-beta as currently administered. Tests are warranted with a capacity to early discriminate responders from non-responders, thereby altering treatment option for the individual patient. In vitro effects of IFN-beta on expression of activation-associated cell surface markers and cytokine production need to be explored in this context. Here we report on the influence in vitro of IFN-beta on blood mononuclear cells (MNC) prepared from MS patients and healthy controls. MNC were subjected to short-term culture in the presence of IFN-beta at concentrations of 100 U/ml and 1000 U/ml. Expression of cell surface molecules CD40, CD69, CD80, CD86, CD95 and HLA-DR was measured by flow cytometry. IL-10 and IL-12 p40 production in culture supernatants was measured by ELISA. MNC exposed to IFN-beta in vitro enhanced expression of the co-stimulatory CD80, CD86, the early activation antigen CD69 and the cell death receptor CD95. Expression of CD40 and HLA-DR was not influenced. IFN-beta increased IL-10 but suppressed IL-12 p40 production. In vitro effects of IFN-beta on MNC were similar in MS patients and in healthy subjects, except that IFN-beta-induced augmentation of CD86 and CD69 expression was less pronounced in MS, in particular in untreated MS patients. Individual MS patients clearly responded differently to IFN-beta in vitro in comparison with the majority of patients in this cross-sectional study. In conclusion, anti-inflammatory effects of IFN-beta on blood MNC include augmentation of IL-10 production and suppression of IL-12 p40 production, which are accompanied by enhancement of CD69, CD80, CD86 and CD95 expression. The less pronounced IFN-beta-induced effects on CD86 and CD69 expression in MS vs controls might reflect a defect in immunoregulation in MS. Larger groups should be evaluated, and follow-up studies performed in MS patients before/during IFN-beta treatment in relation to clinical outcome measures to evaluate the usefulness of these markers for possible differentiation between responders and non-responders to IFN-beta treatment.