title: Transforming growth factor-beta 1 suppresses autoantigen-induced expression of pro-inflammatory cytokines but not of interleukin-10 in multiple sclerosis and myasthenia gravis.
abstract: Multiple sclerosis (MS) is associated with high levels of circulating T lymphocytes that respond to the myelin antigens myelin basic protein (MBP) and proteolipid protein (PLP) by producing various cytokines including interferon-gamma (IFN-gamma) that makes MS worse and transforming growth factor-beta (TGF-beta), an endogenously produced immunosuppressant that might act beneficially. To further define the role of TGF-beta in MS, we examined the effects of recombinant TGF-beta 1 (rTGF-beta 1) on autoantigen-mediated regulation of cytokines in MS and myasthenia gravis (MG). Blood mononuclear cells (MNC) were cultivated with or without rTGF-beta 1, and with or without autoantigen or the recall antigen PPD. MNC expressing cytokine mRNA were detected after in situ hybridization with radiolabeled cDNA oligonucleotide probes. Femtogram concentrations of rTGF-beta 1 suppressed MBP-, PLP- and PPD-induced upregulation of IFN-gamma, IL-4, IL-6, tumor necrosis factor-alpha (TNF-alpha), TNF-beta and perforin in MS, and acetylcholine receptor (AChR)-induced augmentation of these pro-inflammatory cytokines in MG, but had no effects on autoantigen- or PPD-induced expression of IL-10 or TGF-beta itself. rTGF-beta 1 also suppressed numbers of myelin antigen-reactive IFN-gamma- and IL-4-secreting cells in MS and AChR-reactive IFN-gamma and IL-4 secreting cells in MG. The selective suppressive effects of TGF-beta 1 on autoantigen-induced upregulation of pro-inflammatory cytokines makes TGF-beta 1 attractive as a treatment alternative in MS and MG.
authors.affiliation: Division of Neurology and Ophthalmology, Karolinska Institute, Huddinge Hospital, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Link
authors.forename: B
authors.initials: B
authors.lastname: He
authors.forename: V
authors.initials: V
authors.lastname: Navikas
authors.forename: W
authors.initials: W
authors.lastname: Palasik
authors.forename: S
authors.initials: S
authors.lastname: Fredrikson
authors.forename: M
authors.initials: M
authors.lastname: Söderström
authors.forename: H
authors.initials: H
authors.lastname: Link
mesh_terms: D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D017403:In Situ Hybridization; D007249:Inflammation; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D009157:Myasthenia Gravis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000096:biosynthesis; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D001324:Autoantigens; D016207:Cytokines; D004676:Myelin Basic Protein; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma