title: Assessing multiple sclerosis activity: is the in vitro production of tumor necrosis factor-alpha, 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.
authors.affiliation: Laboratoire de Recherche Neurologique, CHUV, Lausanne, Switzerland. Myriam.Schluep@chuv.hospvd.ch
authors.forename: M
authors.initials: M
authors.lastname: Schluep
authors.forename: G
authors.initials: G
authors.lastname: van Melle
authors.forename: H
authors.initials: H
authors.lastname: Henry
authors.forename: C
authors.initials: C
authors.lastname: Städler
authors.forename: B
authors.initials: B
authors.lastname: Roth-Wicky
authors.forename: P J
authors.initials: PJ
authors.lastname: Magistretti
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D001247:Asthenia / Q000209:etiology; D001379:Azathioprine / Q000627:therapeutic use; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid; D007136:Immunoglobulins / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016899:Interferon-beta / Q000627:therapeutic use; D007378:Interleukins / Q000096:biosynthesis* / Q000097:blood / Q000134:cerebrospinal fluid; D009103:Multiple Sclerosis / Q000145:classification / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D043025:Oligoclonal Bands; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis* / Q000134:cerebrospinal fluid
chemical_list: D000276:Adjuvants, Immunologic; D000305:Adrenal Cortex Hormones; D007074:Immunoglobulin G; D007136:Immunoglobulins; D007166:Immunosuppressive Agents; D007378:Interleukins; D043025:Oligoclonal Bands; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D001379:Azathioprine