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?

Abstract

Tumor necrosis factor (TNF) alpha, 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) beta 1 a, or corticosteroids (CST). Statistical correlations significantly showed that: (a) AZA lowers TNF-alpha (P = 0.002) and increases IL-4 production (P = 0.0024), and IFN-beta 1 a increases TNF-alpha and decreases IL-4 levels; (b) CST has a negative effect on TNF-alpha, IL-6, and IL-4 synthesis; and (c) AZA, IFN-beta 1 a, and CST diminish IgG OB synthesis (P = 0.001). Although our study of the dynamics of TNF-alpha, 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-alpha (P = 0.04) and IL-6 (P < 0.05) dropped before exacerbation in the presence of AZA. In vitro production of TNF-alpha 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-beta 1 a (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.

Longitudinal interferon-β effects in multiple sclerosis: Differential regulation of IL-10 and IL-17A, while no sustained effects on IFN-γ, IL-4 or IL-13

“…During the course, myelin antigen-induced IL-4 secretion was reduced after three months, which corroborates some previous findings of decreased IL-4 during IFN-β treatment (33,34), while other studies showed no difference (25,35), or increased IL-4 (28,36). The inconsistencies in previous data surely depend on differences in methodology as well as in time points of sampling.…”

Neuroprotection by upregulation of the major histocompatibility complex class I (MHC I) in SOD1G93A mice

“…In our analyses, the group treated with IFN β demonstrated reduced levels of gene transcripts for IL4 compared to the vehicle group. The reduction of IL4 has already been observed in other studies, which demonstrated, in multiple sclerosis models, that treatment with IFN β acts by reducing the expression of such anti-inflammatory cytokine ( Schluep et al, 1999 ; Andersson et al, 2011 ; Kvarnström et al, 2013 ).…”

Interferon-Beta Treatment Differentially Alters TLR2 and TLR4-Dependent Cytokine Production in Multiple Sclerosis Patients

“…The lack of a correlation between the inflammatory mediators and disease severity in this study has already been observed [33, 34]. Our results in untreated patients may suggest that over time this group naturally presents a reduction of inflammatory mediators, but this could have been influenced by the small number in this group.…”