Lack of macrophage migration inhibitory factor protects mice against concanavalin A-induced liver injury

Abstract

Macrophage migration inhibitory factor (MIF) is involved in inflammatory and immune-mediated diseases but the role of MIF in liver injury has not yet been elucidated. We investigated biochemically, histologically and immunologically the character of MIF in concanavalin A (Con A)-induced T-cell-mediated liver injury using MIF knockout (KO) mice and wild-type (WT) mice. MIF KO mice showed significantly decreased serum alanine aminotransferase values and suppressed histological change with massive necrosis of the hepatic parenchymal cells and infiltration of inflammatory cells compared with their WT counterparts. This protection was not mediated by either tumor necrosis factor-alpha or interferon-gamma, which are critical mediators of Con A-induced liver injury, as their serum concentrations were shown to be similar in MIF KO and WT mice. On the other hand, a flow cytometric analysis demonstrated that the number of activated hepatic leukocytes decreased more in the MIF KO mice than in the WT mice. A lack of MIF protected the mice from Con A-induced liver injury. Controlling the MIF activity may be a useful therapeutic strategy for treating such T-cell activation-associated liver diseases as autoimmune hepatitis and viral hepatitis.