Expression and Regulation of Chemokines in Acute Bacterial Pneumonia

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Abstract
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 MlP-1α augment the ability of PMN and alveolar macrophages, respectively, to phagocytose and kill Escherichia coli. In addition, MIP-2 and MlP-1α 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.

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