Neutralization of macrophage inflammatory protein-2 attenuates neutrophil recruitment and bacterial clearance in murine Klebsiella pneumonia.

The role of macrophage inflammatory protein-2 (MIP-2) in bacterial pneumonia was characterized. Mice were challenged with Klebsiella pneumoniae intratracheally, and organs were harvested at 8, 24, and 48 h. Inoculation with K. pneumoniae resulted in the time-dependent expression of MIP-2 mRNA and protein within the lung, which was maximal 48 h after inoculation. Mice were then passively immunized with rabbit anti-murine MIP-2 serum intraperitoneally 2 h before administration of K. pneumoniae. Treatment with anti-MIP-2 serum resulted in a 60% decrease in lung neutrophil (PMNL) influx and a significant increase in K. pneumoniae colony-forming units in both lung and liver homogenates. Finally, treatment with anti-MIP-2 serum decreased early (48-72 h) but not late (after 72 h) survival in animals with Klebsiella pneumonia. This study indicates that MIP-2 is produced during Klebsiella pneumonia and inhibition of MIP-2 bioactivity in vivo results in decreased PMNL influx and lung bacterial clearance in murine Klebsiella pneumonia. MIP-2 is produced during Klebsiella pneumonia and inhibition of MIP-2 bioactivity in vivo results in decreased PMNL influx and lung bacterial clearance in murine Klebsiella pneumonia.