EXPRESSION AND REGULATION OF CHEMOKINES IN BACTERIAL PNEUMONIA

Effective host defense against bacterial invasion is characterized by the vigorous recruitment and activation of inflammatory cells, which i s dependent on the coordinated expression of both pro- and anti-inflam matory cytokines, In this review, we present evidence indicating that both C-X-C and C-C chemokines are integral components of antibacterial host defense, Specifically, in vitro studies indicate that C-X-C chem okines [interleukin-8 (IL-8) and macrophage inflammatory protein 2 (MI P-2)] and the C-C chemokine macrophage inflammatory protein 1 alpha (M IP-1 alpha) augment the ability of polymorphonuclear leukocytes (PMNs) and alveolar macrophages, respectively, to phagocytose and kill Esche richia coli, In addition, the intratracheal instillation of klebsiella pneumoniae in CD-1 mice results in time-dependent production of MIP-2 and MIP-1 alpha, and the inhibition of MIP-2 bioactivity in vivo resu lts in decreases in lung PMN influx, impaired bacterial clearance, and early mortality, Finally, the anti-inflammatory cytokine interleukin- 10 (IL-10) is also expressed within the lung during the evolution of K lebsiella pneumonia, and neutralization of IL-10 in vivo results in en hanced proinflammatory cytokine production, bacterial clearance, and i ncreases in both short- and long-term survival, In conclusion, our stu dies indicate that specific chemokines are important mediators of leuk ocyte recruitment and/or activation in bacterial pneumonia and that th e expression of these chemokines is regulated by endogenously produced IL-10.