The role of macrophage migration inhibitory factor in lethal Listeria monocytogenes infection in mice

Macrophage migration inhibitory factor (MIF) has been characterized as a proinflammatory cytokine. Previous studies have indicated that MIF may play a beneficial role or a detrimental role in microbial infections, depending on pathogens. In this study, we investigated the role of MIF in Listeria monocytogenes infection. The MIF titers increased 6 h after lethal L. monocytogenes infection but not in the sublethal infection. The elimination of bacteria from the spleens and livers was not affected by anti-MIF antibody (Ab) injection in the sublethal infection, whereas anti-MIF Ab treatment rescued mice from the lethal infection, suggesting that MIF plays a deteriorating role in lethal L. monocytogenes infection. Anti-MIF Ab treatment significantly augmented interleukin (IL)-10 production in the spleens and livers 24 h after infection, suggesting that MIF might down-regulate IL-10 production. Although the administration of anti-IL-10 monoclonal Ab showed no significant effect on the bacterial growth in the organs, the bacterial infection was deteriorated by the combined administration of Abs against MIF and IL-10. On the other hand, anti-MIF Ab treatment also increased in the serum cortisol titer 6 h after infection compared with the control immunoglobulin G-injected group. Depletion of endogenous IL-10 decreased serum cortisol titers. These results suggested that IL-10 and cortisol might be involved in the deteriorating effect of MIF on lethal L. monocytogenes infection.