title: Expression and regulation of chemokines in bacterial pneumonia.
abstract: 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.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0360, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Standiford
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: M J
authors.initials: MJ
authors.lastname: Greenberger
authors.forename: L L
authors.initials: LL
authors.lastname: Laichalk
authors.forename: R M
authors.initials: RM
authors.lastname: Strieter
mesh_terms: D000818:Animals; D018925:Chemokines / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology; D051379:Mice; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000378:metabolism
chemical_list: D018925:Chemokines