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Protective role of interleukin-1 in mycobacterial infection in IL-1 alpha/beta double-knockout mice.

Abstract
To understand the role of the proinflammatory cytokine interleukin-1 (IL-1) in mycobacterial inflammation, IL-1 alpha/beta double-knockout (KO) mice were produced. These mice were infected with either Mycobacterium tuberculosis H37Rv by the airborne route using an airborne infection apparatus, and their capacities to control mycobacterial growth, granuloma formation, cytokine, and nitric oxide (NO) production were examined. The IL-1 alpha/beta mice developed significantly larger (p < 0.01) granulomatous, but not necrotic, lesions in their lungs than wild-type (WT) mice after infection with H37Rv. Inflammatory lesions, but not granulomas, were observed in spleen and liver tissues from both IL-1 alpha/beta KO and wild-type mice. Granulomatous lesion development in IL-1 alpha/beta KO mice was not significantly inhibited by treatment with exogenous recombinant IL-1 alpha/beta. Compared with wild-type mice, splenic IFN-gamma and IL-12 levels were within the normal range. NO production by cultured alveolar macrophages from IL-1 alpha/beta KO mice was lower than in wild-type mice but were increased by the addition of recombinant IL-1 alpha/beta. Our data clearly indicate that IL-1 is important for the generation of early-phase protective immunity against mycobacterial infection.
AuthorsH Yamada, S Mizumo, R Horai, Y Iwakura, I Sugawara
JournalLaboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 80 Issue 5 Pg. 759-67 (May 2000) ISSN: 0023-6837 [Print] United States
PMID10830786 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Interleukin-1
  • Nitric Oxide
  • Interferon-gamma
Topics
  • Animals
  • Interferon-gamma (physiology)
  • Interleukin-1 (deficiency, physiology)
  • Mice
  • Mice, Knockout
  • Mycobacterium Infections (immunology, pathology)
  • Mycobacterium bovis (immunology)
  • Nitric Oxide (physiology)
  • Reverse Transcriptase Polymerase Chain Reaction

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