Role of macrophage migration inhibitory factor in ovalbumin-induced asthma in rats

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine and reportedly counteracts the anti-inflammatory effect of endogenous glucocorticoids. There have been only a few reports that demonstrate a potential link between MIF and bronchial asthma. In an attempt to further clarify the precise role of MIF in asthma, we examined the effect of anti-MIF antibody on airway inflammation and airway hyperresponsiveness in an ovalbumin-immunized rat asthma model. Actively immunized Brown-Norway rats received ovalbumin inhalation with or without treatment of anti-MIF antibody. The levels of MIF in bronchoalveolar lavage fluid were significantly elevated after the ovalbumin challenge. An immunohistochemical study revealed positive immunostaining for MIF in bronchial epithelium, even in nonsensitized rats, and the MIF staining in bronchial epithelium was enhanced after the ovalbumin challenge. Anti-MIF antibody significantly decreased the numbers of total cells, neutrophils, and eosinophils in the bronchoalveolar lavage fluid of the ovalbumin-challenged rats, and also attenuated the ovalbumin-induced airway hyperresponsiveness to ovalbumin and methacholine. However, anti-MIF antibody did not affect the level of serum ovalbumin-specific IgE, suggesting that anti-MIF antibody did not suppress immunization itself. These results indicate that MIF plays a crucial role in airway inflammation as well as airway hyperresponsiveness in asthma.