title: Antagonistic effects of endogenous and exogenous TGF-beta and TNF on auto-immune diseases in mice.
abstract: Injection of transforming growth factor beta 1 (TGF-beta 1) for five days during the late phase of the immunization process leading either to collagen type II induced arthritis (CIA) or to experimental allergic encephalomyelitis (EAE) protects against the development of these auto-immune diseases. Tumor necrosis factor alpha (TNF-alpha) injected during this same interval aggrevates CIA. In addition, anti-TGF-beta exacerbates and anti-TNF protects against CIA, acute and relapsing EAE, suggesting an important regulatory role for the endogenous production of the two cytokines on the severity of these diseases. More detailed studies about the mechanism of action of TGF-beta in acute EAE show that there is no detectable effect of TGF-beta on the development of sensitized T cells in vivo, as assayed by the proliferative responses of T cells from lymph nodes and peripheral blood to myelin antigens. Nevertheless, the number of lymphoid cells infiltrating the central nervous tissue is much greater in untreated than in TGF-beta-treated, protected mice. We conclude that it is likely that TGF-beta protects against experimental auto-immune diseases by interfering with the entry of lymphoid cells into the target organs through inhibition of the upregulation of adhesion molecule expression on endothelial cells, and with subsequent inflammatory processes inside the target organs by antagonizing both the production and the effects of TNF.
authors.affiliation: Department of Pathology, NYU School of Medicine, NY 10016.
authors.forename: L
authors.initials: L
authors.lastname: Santambrogio
authors.forename: G M
authors.initials: GM
authors.lastname: Hochwald
authors.forename: C H
authors.initials: CH
authors.lastname: Leu
authors.forename: G J
authors.initials: GJ
authors.lastname: Thorbecke
mesh_terms: D000818:Animals; D001168:Arthritis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003094:Collagen / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology
chemical_list: D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen