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


CONCLUSIONS
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.
Li
Wei-Dong
WD
Department of Pharmacology, Health Science Center of Peking University, Beijing 100083, China. wdlee@btamail.net.cn
Ran
Guo-Xia
GX
Teng
Hui-Ling
HL
Lin
Zhi-Bin
ZB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology*; D000077339:Leflunomide; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D015850:Interleukin-6; D007555:Isoxazoles; D014409:Tumor Necrosis Factor-alpha; D000077339:Leflunomide