REDUCTION OF ARTHRITIS AND PNEUMONITIS IN MOTH-EATEN MICE BY SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTOR

Objective. To determine the effects of anti-tumor necrosis factor (ant i-TNF) therapy in the inflammatory and autoimmune disease in motheaten (me/me) mice, which exhibit a Pas apoptosis signaling defect. Methods . Arthritis, pneumonitis, and mortality were analyzed in me/me mice tr eated with a novel, soluble, dimeric TNF receptor I (sTNFRI) molecule capable of high-affinity binding and neutralization of TNF alpha. Resu lts. Soluble TNFRI reduced serum levels of TNF alpha and led to a 2-fo ld increase in the lifespan of me/me mice, compared with the control t reatment group, The treatment also reduced the development of the ''mo theaten'' skin patches and alleviated pneumonitis and inflammatory les ions in the extremities of me/me mice compared with controls, However, the serum levels of IgM and IgM anti-double-stranded DNA autoantibody were comparable to those of untreated control mice. Conclusion. TNF a lpha is an important cytokine involved in the pathogenesis of inflamma tory disease in me/me mice, resulting in tissue damage and early morta lity, Therapies directed at blocking TNF/TNFR interactions, such as th e sTNFRI used in these experiments, may be effective in diseases assoc iated with apoptosis defects leading to overutilization of the TNF/TNF R pathway.