Effect of leflunomide on immunological liver injury in mice.

Abstract

To study the effect of leflunomide on immunological liver injury (ILI) in mice. ILI was induced by tail vein injection of 2.5 mg Bacillus Calmette-Guerin (BCG), and 10 d later with 10 microg lipopolysaccharide (LPS) in 0.2 mL saline (BCG+LPS). The alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO) level in plasma and molondiadehyde (MDA), glutathione peroxidase (GSHpx) in liver homogenate were assayed by spectroscopy. The serum content of tumor necrosis factors-alpha (TNF-alpha) was determined by ELISA. Interleukin-1 (IL-1), interleukin-2 (IL-2) and Concanavalin A (ConA)-induced splenocyte proliferation response were determined by methods of (3)H-infiltrated cell proliferation. Leflunomide (4, 12, 36 mg.kg(-1)) was found to significantly decrease the serum transaminase (ALT, AST) activity and MDA content in liver homogenate, and improve reduced GSHpx level of liver homogenate. Leflunomide (4, 12, 36 mg.kg(-1)) significantly lowered TNF-alpha and NO level in serum, and IL-1 produced by intraperitoneal macrophages(PMphi). Moreover, the decreased IL-2 production and ConA-induced splenocyte proliferation response were further inhibited. These findings suggested that leflunomide had significant protective action on ILI in mice.