Role of macrophage migration inhibitory factor (MIF) in allergic and endotoxin-induced airway inflammation in mice

MACROPHAGE migration inhibitory factor (MIF) has recently been forwarded as a critical regulator of inflammatory conditions, and it has been hypothesi zed that MIF may have a role in the pathogenesis of asthma and chronic obst ructive pulmonary disease (COPD). Hence, we examined effects of MIF immunon eutralization on the development of allergen-induced eosinophilic inflammat ion as well as on lipopolysaccaride (LPS)-induced neutrophilic inflammation in lungs of mice. Anti-MIF serum validated with respect to MIF neutralizin g capacity or normal rabbit serum (NRS) was administered i.p. repeatedly du ring allergen aerosol exposure of ovalbumin (OVA)-immunized mice in an esta blished model of allergic asthma, or once before Instillation of a minimal dose of LPS into the airways of mice, a tentative model of COPD. Anti-MIF t reatment did not affect the induced lung tissue eosinophilia or the cellula r composition of bronchoalveolar lavage fluid (BALF) in the asthma model. L ikewise, anti-MIF treatment did not affect the LPS-induced neutrophilia in lung tissue, BALL, or blood, nor did it reduce BALL levels of tumor necrosi s factor-alpha (TNF-alpha) and macrophage inflammatory protein-1 alpha (MIP -1 alpha). The present data suggest that MIF is not critically important fo r allergen-induced eosinophilic, and LPS-induced neutrophilic responses in lungs of mice. These findings do not support a role of MIF inhibition in th e treatment of inflammatory respiratory diseases.