More MS news articles for Nov 2001

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

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11696016&dopt=Abstract

Acta Neurol Scand 2001 Nov;104(5):249-56
Huang YM, Hussien Y, Jin YP, Soderstrom M, Link H.
Neuroimmunology Unit, Division of Neurology, Karolinska Institute, SE-141 86 Huddinge University Hospital, Stockholm, Sweden.

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.
 

PMID: 11696016 [PubMed - in process]