Therapeutic effect of anti-macrophage inflammatory protein 2 antibody on influenza virus-induced pneumonia in mice

We investigated the effect of anti-macrophage inflammatory protein 2 immuno globulin G (aMIP 2 Igc) on the progression of influenza virus-induced pneum onia in mice. When mice were infected with a mouse lung-adapted strain of i nfluenza A/PR/8/34 virus by intranasal inoculation, neutrophil counts in th e bronchoalveolar lavage fluid (BALF) increased in parallel with the kineti cs of MIP-2 production, which peaked 2 days after infection. After intracut aneous injection of a dose of 10 or 100 mu g of aMIP-2 Ige once a day on da ys 0 and 1, neutrophil counts in BALF on day 2 were reduced to 49 or 37%, r espectively, of the value in the control infected mice administered anti-pr otein A IgG. The antibody administration also improved lung pathology witho ut affecting virus replication. Furthermore, by prolonged administration,vi th a higher or lower dose for up to 5 days, body weight loss became slower and finally 40% of mice in both treatment groups survived potentially letha l pneumonia. These findings suggest that MIP 2-mediated neutrophil infiltra tion during the early phase of infection might play an important role in lu ng pathology. Thus, MIP-2 was considered to be a novel target for intervent ion therapy in potentially lethal influenza virus pneumonia in mice.