Am. J. Respir. Crit. Care Med., Volume 158, Number 2, August 1998, 573-579

Effect of Anti-Macrophage Migration Inhibitory Factor Antibody on Lipopolysaccharide-induced Pulmonary Neutrophil Accumulation

HIRONI MAKITA, MASAHARU NISHIMURA, KENJI MIYAMOTO, TSUYOSHI NAKANO, YOSHINORI TANINO, JUNICHI HIROKAWA, JUN NISHIHIRA, and YOSHIKAZU KAWAKAMI

First Department of Medicine and Central Research Institute, Hokkaido University School of Medicine, Sapporo, Japan

Macrophage migration inhibitory factor (MIF) is a recently rediscovered 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)-induced 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 observation of the number of neutrophils per alveolus, the activity of myeloperoxidase of the lung tissue, and cell differentiation of neutrophils in bronchoalveolar lavage (BAL) fluid. The increased level of macrophage inflammatory protein-2, a powerful neutrophil chemokine, in BAL fluid was also significantly attenuated by pretreatment with the anti-MIF antibody as compared with the control group. Additionally, positive immunostaining for MIF was observed in bronchial epithelial cells and alveolar macrophages, and Northern blot analysis of lung tissues demonstrated increased MIF mRNA 24 h after LPS injection. These data suggest that the anti-MIF antibody has therapeutic potential for the treatment of acute lung injury by suppressing the level of neutrophil chemokine in the lungs.

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