Expression and Regulation of Chemokines in Acute Bacterial Pneumonia

Effective host defense against bacterial invasion is characterized by the vigorous recruitment and activation of inflammatory cells, which are dependent upon the coordinated expression of both pro- and anti-inflammatory cytokines. In this study, we have demonstrated that both C-X-C and C-C chemokines are integral components of antibacterial host defense. Specifically, studies in vitro indicate that macrophage inflammatory protein-2 (MIP-2) and MIP-1 alpha augment the ability of PMN and alveolar macrophages, respectively, to phagocytose and kill Escherichia coli. In addition, MIP-2 and MIP-1 alpha are expressed within the lung in response to the intratracheal instillation of Klebsiella pneumoniae, and the inhibition of MIP-2 bioactivity in vivo results in decreases in lung PMN influx, bacterial clearance, and early survival. Finally, the anti-inflammatory cytokine interleukin-10 (IL-10) is also expressed within the lung during the evolution of Klebsiella pneumonia, and neutralization of IL-10 results in enhanced proinflammatory cytokine production, bacterial clearance, and increases in both short- and long-term survival. In conclusion, our studies indicate that specific chemokines are important mediators of leukocyte recruitment and/or activation in bacterial pneumonia, and that the expression of these chemokines is regulated by endogenously produced IL-10.