Interleukin-17 and lung host defense against Klebsiella pneumoniae infection

Am J Respir Cell Mol Biol. 2001 Sep;25(3):335-40. doi: 10.1165/ajrcmb.25.3.4424.

Abstract

Bacterial pneumonia remains an important cause of morbidity and mortality worldwide, especially in immune-compromised patients. Cytokines and chemokines are critical molecules expressed in response to invading pathogens and are necessary for normal lung bacterial host defenses. Here we show that interleukin (IL)-17, a novel cytokine produced largely by CD4+ T cells, is produced in a compartmentalized fashion in the lung after challenge with Klebsiella pneumoniae. Moreover, overexpression of IL-17 in the pulmonary compartment using a recombinant adenovirus encoding murine IL-17 (AdIL-17) resulted in the local induction of tumor necrosis factor-alpha, IL-1beta, macrophage inflammatory protein-2, and granulocyte colony-stimulating factor (G-CSF); augmented polymorphonuclear leukocyte recruitment; and enhanced bacterial clearance and survival after challenge with K. pneumoniae. However, simultaneous treatment with AdIL-17 provided no survival benefit after intranasal K. pneumoniae challenge. These data show that IL-17 may have a role in priming for enhanced chemokine and G-CSF production in the context of lung infection and that optimally timed gene therapy with IL-17 may augment host defense against bacterial pneumonia.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Chemokine CXCL2
  • Chemokines / metabolism
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Humans
  • Interleukin-1 / metabolism
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Klebsiella Infections / immunology*
  • Klebsiella pneumoniae / metabolism*
  • Lung / chemistry
  • Lung / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pneumonia, Bacterial / immunology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Chemokine CXCL2
  • Chemokines
  • Cxcl2 protein, mouse
  • Interleukin-1
  • Interleukin-17
  • Tumor Necrosis Factor-alpha
  • Granulocyte Colony-Stimulating Factor