IN-VITRO CYTOKINE PROFILES AS INDICATORS OF RELAPSE ACTIVITY AND CLINICAL COURSE IN MULTIPLE-SCLEROSIS

In vitro production of tumor necrosis factor-alpha (TNF-alpha), interl eukin-2 (IL-2), IL-4, IL-6, IL-10 and oligoclonal IgG (IgG OB) was eva luated in the aim to investigate their Profile in correlation with mul tiple sclerosis (MS) clinical activity and clinical course. Whole bloo d stimulation with lipopolysaccharide or concanavalin A was Performed in 61 patients presenting with relapsing-remitting relapsing-progressi ve or chronic progressive MS; treatments received were: none, azathiop rine (AZA), cyclosporin, cyclophosphamide, subcutaneous interferon-bet a 1a (IFN-beta 1a) and corticosteroids (CST). The cinetics of cytokine production showed that (i) in the absence of treatment, TNF-alpha and IL-6 dropped respectively after and during the periods surrounding re lapse, while IL-4 was increasing before and IL-IO after relapse; (ii) with AZA, TNF-alpha and IL-6 lowered before exacerbation, IL-4 prolong ed high levels after and IL-IO before relapse; (iii) with IFN-beta 1a IL-IO was already increasing before relapse, and TNF-alpha was higher after relapse. When cytokine levels were analysed independently from M S clinical activity, the use of AZA inhibited IgG OB and TNF-alpha syn thesis (P=0.002) but increased IL-4 (P=0.0024), whereas IFN-beta la st imulated TNF-alpha and inhibited IgG OB and IL-4 production. CST inhib ited TNF-alpha, IL-6, IL-4 and IgG OB synthesis. This study stresses b oth the weight of clinical parameters and of methodology used in resul ts obtained in cytokine analysis in MS.