Assessing multiple sclerosis activity: is the in vitro production of tumornecrosis factor-alpha, interleukins 2, 6, 4, and 10, and immunoglobulin G of value?

Tumor necrosis factor (TNF) alpha, interleukins (IL) 2, 4, 6, and 10, and I gG oligoclonal bands (IgG OB) in vitro production was assessed, after whole -blood stimulation with lipopolysaccharide or concanavalin A, in 61 patient s presenting with relapsing-remitting, relapsing-progressive, or chronic pr ogressive multiple sclerosis. Multiple sclerosis patients were receiving no treatment or azathioprine (AZA), cyclosporin, cyclophosphamide, subcutaneo us interferon (IFN) beta 1a, or corticosteroids (CST). Statistical correlat ions significantly showed that: (a) AZA lowers TNF-alpha (P = 0.002) and in creases IL-4 production (P = 0.0024), and IFN-beta 1a increases TNF-alpha a nd decreases IL-4 levels; (b) CST has a negative effect on TNF-alpha, IL-6, and IL-4 synthesis; and (c) AZA, IFN-beta 1a, and CST diminish IgG OB synt hesis (P = 0.001). Although our study of the dynamics of TNF-alpha, IL-2, I L-4, IL-6, and IL-IO in vitro production generally found no statistically s ignificant correlations (partly explained by the limited number of values i n the various groups), IL-6 was shown to drop during the periods surroundin g relapse (P = 0.05) in the absence of treatment, while TNF-alpha (P = 0.04 ) and IL-6 (P < 0.05) dropped before exacerbation in the presence of AZA. I n vitro production of TNF-alpha was closely and positively correlated with that of IL-6, independently of clinical features. The enhanced production o f IL-IO detected before or at relapse with AZA and IFN-beta 1a (trends) may interfere with initiation of the immune reaction and with the development of new CNS lesions. Some discrepancies with previously published results st ress the difficulties in studying the slate of stimulation of different pop ulations of leukocytes by using a variety of in vitro stimuli and in establ ishing a correlation between mRNA studies and the amount of final or active protein produced.