Standiford T J, Kunkel S L, Greenberger M J, Laichalk L L, Strieter R M
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0360, USA.
J Leukoc Biol. 1996 Jan;59(1):24-8. doi: 10.1002/jlb.59.1.24.
Effective host defense against bacterial invasion is characterized by the vigorous recruitment and activation of inflammatory cells which is dependent on the coordinated expression of both pro and anti-inflammatory 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 chemokines [interleukin-8 (IL-8) and macrophage inflammatory protein 2 (MIP-2) and the C-C chemokine macrophage inflammatory protein 1 alpha (MIP-1 alpha) augment the ability of polymorphonuclear leukocytes (PMNs) and alveolar macrophages, respectively, to phagocytose and kill Escherichia 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 results 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 Klebsiella pneumonia, and neutralization of IL-10 in vivo 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.
