Assessing multiple sclerosis activity: Is the in vitro production of tumor necrosis factor-α, interleukins 2, 6, 4, and 10, and immunoglobulin G of value?

Tumor necrosis factor (TNF) α, interleukins (IL) 2, 4, 6, and 10, and IgG oligoclonal bands (IgG OB) in vitro production was assessed, after whole-blood stimulation with lipopolysaccharide or concanavalin A, in 61 patients presenting with relapsing-remitting, relapsing-progressive, or chronic progressive multiple sclerosis. Multiple sclerosis patients were receiving no treatment or azathioprine (AZA), cyclosporin, cyclophosphamide, subcutaneous interferon (IFN) β1a, or corticosteroids (CST). Statistical correlations significantly showed that: (a) AZA lowers TNF-α (P = 0.002) and increases IL-4 production (P = 0.0024), and IFN-β1a increases TNF-α and decreases IL-4 levels; (b) CST has a negative effect on TNF-α, IL-6, and IL-4 synthesis; and (c) AZA, IFN-β1a, and CST diminish IgG OB synthesis (P = 0.001). Although our study of the dynamics of TNF-α, IL-2, IL-4, IL-6, and IL-10 in vitro production generally found no statistically significant correlations (partly explained by the limited number of values in the various groups), IL-6 was shown to drop during the periods surrounding relapse (P = 0.05) in the absence of treatment, while TNF-α (P = 0.03) and IL-6 (P < 0.05) dropped before exacerbation in the presence of AZA. In vitro production of TNF-α was closely and positively correlated with that of IL-6, independently of clinical features. The enhanced production of IL-10 detected before or at relapse with AZA and IFN-β1a (trends) may interfere with initiation of the immune reaction and with the development of new CNS lesions. Some discrepancies with previously published results stress the difficulties in studying the state of stimulation of different populations of leukocytes by using a variety of in vitro stimuli and in establishing a correlation between mRNA studies and the amount of final or active protein produced.