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), interleukin-2 (IL-2), IL-4, IL-6, IL-10 and oligoclonal IgG (IgG OB) was evaluated in the aim to investigate their profile in correlation with multiple sclerosis (MS) clinical activity and clinical course. Whole blood stimulation with lipopolysaccharide or concanavalin A was performed in 61 patients presenting with relapsing-remitting, relapsing-progressive or chronic progressive MS; treatments received were: none, azathioprine (AZA), cyclosporin, cyclophosphamide, subcutaneous interferon-beta 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 relapse, while IL-4 was increasing before and IL-10 after relapse; (ii) with AZA, TNF-alpha and IL-6 lowered before exacerbation, IL-4 prolonged high levels after and IL-10 before relapse; (iii) with IFN-beta 1a, IL-10 was already increasing before relapse, and TNF-alpha was higher after relapse. When cytokine levels were analysed independently from MS clinical activity, the use of AZA inhibited IgG OB and TNF-alpha synthesis (P = 0.002) but increased IL-4 (P = 0.0024), whereas IFN-beta 1a stimulated TNF-alpha and inhibited IgG OB and IL-4 production. CST inhibited TNF-alpha, IL-6, IL-4 and IgG OB synthesis. This study stresses both the weight of clinical parameters and of methodology used in results obtained in cytokine analysis in MS.