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.
Keywords:
(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.