Prevention of spontaneous polyarthritis in NZB/KN mice by treatment with a novel thiazole derivative, SM-8849.

Abstract

NZB/KN mice spontaneously develop polyarthritis, characterized by infiltration of inflammatory cells into the synovium and destructive damage of articular cartilage and bone. This study was performed to elucidate the effects of a novel thiazole derivative (SM-8849; (4-[1-(2-fluoro-4-biphenylyl)-ethyl]-2-methylamino thiazole) in comparison with the cyclooxygenase inhibitor, indomethacin, on disease development and immune disorders in NZB/KN mice. Mice were treated with SM-8894 (50 mg/kg) or indomethacin (2 mg/kg), starting from two months of age, for seven months. Indomethacin had no inhibitory effect on joint lesions in this model. In contrast, SM-8849 was effective in arresting the progression of arthritis, as confirmed by histologic and radiographic studies. Moreover, SM-8849, but not indomethacin, suppressed rheumatoid factor production. In addition, the population of CD5+ B cells in the peritoneal cavity and spleen was reduced with SM-8849 treatment. These findings suggest that NZB/KN mice are of use in the evaluation of intrinsic antiarthritic activity, independently of cyclooxygenase inhibition. Additionally, the therapeutic value of SM-8849 is strongly suggested by its efficacy in this model.

• Authors: F Nishikaku, K Nakamura, S Kashiwazaki, Y Koga
• Journal: Drugs under experimental and clinical research (Drugs Exp Clin Res) Vol. 20 Issue 3 Pg. 85-92 ( 1994) ISSN: 0378-6501 [Print] Switzerland
• PMID: 7956720 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Biphenyl Compounds
• Thiazoles
• 4-(1-(2-fluoro-4-biphenyl)ethyl)-2-methylaminothiazole
• Rheumatoid Factor
• Indomethacin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Arthritis (diagnostic imaging, pathology, prevention & control)
• Biphenyl Compounds (therapeutic use)
• Foot (diagnostic imaging, pathology)
• Hindlimb (diagnostic imaging, pathology)
• Indomethacin (therapeutic use)
• Lymphocyte Count
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred Strains
• Peritoneal Cavity (cytology)
• Radiography
• Rheumatoid Factor (metabolism)
• Spleen (cytology)
• Thiazoles (therapeutic use)