Reduction of arthritis and pneumonitis in motheaten mice by soluble tumor necrosis factor receptor.

Academic Article

Abstract

  • OBJECTIVE: To determine the effects of anti-tumor necrosis factor (anti-TNF) therapy in the inflammatory and autoimmune disease in motheaten (me/me) mice, which exhibit a Fas apoptosis signaling defect. METHODS: Arthritis, pneumonitis, and mortality were analyzed in me/me mice treated with a novel, soluble, dimeric TNF receptor I (sTNFRI) molecule capable of high-affinity binding and neutralization of TNFalpha. RESULTS: Soluble TNFRI reduced serum levels of TNFalpha and led to a 2-fold increase in the lifespan of me/me mice, compared with the control treatment group. The treatment also reduced the development of the "motheaten" skin patches and alleviated pneumonitis and inflammatory lesions 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: TNFalpha is an important cytokine involved in the pathogenesis of inflammatory disease in me/me mice, resulting in tissue damage and early mortality. Therapies directed at blocking TNF/TNFR interactions, such as the sTNFRI used in these experiments, may be effective in diseases associated with apoptosis defects leading to overutilization of the TNF/TNFR pathway.

    • Keywords

  • Alopecia, Animals, Antigens, CD, Apoptosis, Arthritis, Autoantibodies, Binding, Competitive, Carrier Proteins, Dimerization, Longevity, Mice, Mice, Inbred C3H, Mice, Mutant Strains, Mutation, Pneumonia, Polyethylene Glycols, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Type I, Recombinant Proteins, Survival Analysis, Tumor Necrosis Factor Decoy Receptors, Tumor Necrosis Factor-alpha

    • Author List

  • Su X; Zhou T; Yang P; Edwards CK; Mountz JD

    • Start Page

  • 139

    • End Page

  • 149

    • Volume

  • 41