EFFECT OF ANTIMACROPHAGE MIGRATION-INHIBITORY FACTOR ANTIBODY ON LIPOPOLYSACCHARIDE-INDUCED PULMONARY NEUTROPHIL ACCUMULATION

Macrophage migration inhibitory factor (MIF) is a recently rediscovere d pro-inflammatory cytokine that has the unique potential to override the anti-inflammatory action of glucocorticoids. Since recent reports suggest the pivotal role of MIF in acute lung injury, we examined the protective effect of anti-MIF antibody on lipopolysaccharide (LPS)-ind uced acute lung injury in rats. Rats were injected with LPS (7 mg/kg) intraperitoneally with or without pretreatment with anti-MIF antibody. The anti-MIF antibody significantly attenuated LPS-induced migration of neutrophils to the lungs at 4 and 24 h as demonstrated by observati on of the number of neutrophils per alveolus, the activity of myeloper oxidase of the lung tissue, and cell differentiation of neutrophils in bronchoalveolar lavage (BAL) fluid. The increased level of macrophage inflammatory protein-a, a powerful neutrophil chemokine, in BAL fluid was also significantly attenuated by pretreatment with the anti-MIF a ntibody as compared with the control group. Additionally, positive imm unostaining for MIF was observed in bronchial epithelial cells and alv eolar macrophages, and Northern blot analysis of lung tissues demonstr ated increased MIF mRNA 24 h after LPS injection. These data suggest t hat the anti-MIF antibody has therapeutic potential for the treatment of acute lung injury by suppressing the level of neutrophil chemokine in the lungs.