Antagonistic Effects of Endogenous and Exogenous Tgf-$sZ and Tnf on Auto-immune Diseases in Mice

Abstract

Injection of transforming growth factor $sZ₁ (TGF-$sZ₁) 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 a (TNF-$aL) injected during this same interval aggrevates CIA. In addition, anti-TGF-$sZ 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-$sZ in acute EAE show that there is no detectable effect of TGF-$sZ 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-$sZ-treated, protected mice. We conclude that it is likely that TGF-$sZ 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.