IFN-beta may modify the clinical course of multiple sclerosis (MS) but is n
ot 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 treatme
nt option for the individual patient. In vitro effects of IFN-beta on expre
ssion of activation-associated cell surface markers and cytokine production
need to be explored in this context. Here we report on the influence in vi
tro of IFN-beta on blood mononuclear cells (MNC) prepared from MS patients
and healthy controls. MNC were subjected to shortterm culture in the presen
ce of IFN-beta at concentrations of 100 U/ml and 1000 U/ml. Expression of c
ell 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 w
as measured by ELISA. MNC exposed to IFN-beta in vitro enhanced expression
of the costimulatory 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 eff
ects 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 wa
s less pronounced in MS, in particular in untreated MS patients. Individual
MS patients clearly responded differently to IFN-beta in vitro in comparis
on with the majority of patients in this cross-sectional study. In conclusi
on, anti-inflammatory effects of IFN-beta on blood MNC include augmentation
of IL-10 production and suppression of IL-12 p40 production, which are acc
ompanied by enhancement of CD69, CD80, CD86 and CD95 expression. The less p
ronounced IFN-beta -induced effects on CD86 and CD69 expression in MS vs co
ntrols might reflect a defect in immunoregulation in MS. Larger groups shou
ld be evaluated, and follow-up studies performed in MS patients before/duri
ng IFN-beta treatment in relation to clinical outcome measures to evaluate
the usefulness of these markers for possible differentiation between respon
ders and non-responders to IFN-beta treatment.