Dynamic effects of leflunomide on IL-1, IL-6, and TNF-alpha activity produced from peritoneal macrophages in adjuvant arthritis rats

Abstract

Aim: To investigate the effects of leflunomide (LEF) on modulating interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor- alpha (TNF-alpha) production induced by lipopolysaccharide (LPS) in peritoneal macrophages (PMphi) in adjuvant arthritis rats and elucidate the possible mechanisms of antiinflammatory and antirheumatoid effects of LEF.

Methods: Freund's complete adjuvant was injected in the hind footpad of rats to induce adjuvant arthritis (AA) rat model. The PMphi samples were taken at different time after medication. IL-1, IL-6, and TNF-alpha activities released from PMphi were measured by ELISA method or bioassay method.

Results: Production of IL-1, IL-6, and TNF-alpha was increased in the culture supernatant of PMphi in AA model rat. LEF could inhibit LPS-induced release of IL-1 and TNF-alpha from PMphi of the AA rats and the inhibitory effects were extremely rapid. LEF (10, 25 mg/kg) administrated for 21d could inhibit IL-6 release from PMphi in AA rats.

Conclusion: The antiinflammatory mechanisms of LEF in AA rats might be related to inhibitory level of IL-1, IL-6, and TNF-alpha from PMphi in vivo.