Multiple sclerosis: deficient in vitro responses of blood mononuclear cells to IFN‐β

IFN‐β 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‐β 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‐β 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‐β on blood mononuclear cells (MNC) prepared from MS patients and healthy controls. MNC were subjected to short‐term culture in the presence of IFN‐β 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‐βin 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‐β increased IL‐10 but suppressed IL‐12 p40 production. In vitro effects of IFN‐β on MNC were similar in MS patients and in healthy subjects, except that IFN‐β‐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‐βin vitro in comparison with the majority of patients in this cross‐sectional study. In conclusion, anti‐inflammatory effects of IFN‐β 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‐β‐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‐β treatment in relation to clinical outcome measures to evaluate the usefulness of these markers for possible differentiation between responders and non‐responders to IFN‐β treatment.

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