Suppression of murine collagen-induced arthritis by treatment with a novel thiazole derivative, SM-8849

Immunopharmacology. Jan-Feb 1993;25(1):65-74. doi: 10.1016/0162-3109(93)90031-k.

Abstract

The antiarthritic activity of a novel thiazole derivative, SM-8849, was compared with that of indomethacin and D-penicillamine, in mice with collagen-induced arthritis. SM-8849 reduced the incidence and severity of disease in collagen-immunized mice, as assessed by clinical observation. This efficacy was also confirmed by radiographic and histologic studies. Indomethacin produced an apparent reduction of the clinical score, but had only a marginal effect on bone destruction. D-penicillamine did not produce any improvement. Unlike indomethacin and D-penicillamine, SM-8849 reduced the serum levels of anti-type II collagen antibodies. Flow cytometric analysis of spleen cells from arthritic mice revealed an increase in T cells expressing activation antigens (class II antigens) in comparison with normal mice. Treatment with SM-8849, but not indomethacin or D-penicillamine, prevented the increase in Ia-bearing T cells. The results suggest that an effect of SM-8849 on immunocompetent cells may be responsible for the antiarthritic activity of the compound, and this would distinguish its action from that of traditional antirheumatic drugs.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / pathology
  • Biphenyl Compounds / pharmacology
  • Biphenyl Compounds / therapeutic use*
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / drug effects
  • Bone and Bones / pathology
  • Cartilage, Articular / pathology
  • Collagen / immunology
  • Flow Cytometry
  • Histocompatibility Antigens Class II / analysis
  • Immunoglobulin M / blood
  • Indomethacin / pharmacology
  • Indomethacin / therapeutic use
  • Male
  • Mice
  • Mice, Inbred DBA
  • Penicillamine / pharmacology
  • Penicillamine / therapeutic use
  • Radiography
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use*

Substances

  • Biphenyl Compounds
  • Histocompatibility Antigens Class II
  • Immunoglobulin M
  • Thiazoles
  • 4-(1-(2-fluoro-4-biphenyl)ethyl)-2-methylaminothiazole
  • Collagen
  • Penicillamine
  • Indomethacin