title: Interleukin-6 gene-deficient mice show impaired defense against pneumococcal pneumonia.
abstract: Induction of pneumonia in C57Bl/6 mice by intranasal inoculation with 10(6) cfu of Streptococcus pneumoniae resulted in sustained expression of interleukin (IL)-6 mRNA in lungs and increases in lung and plasma IL-6 concentrations. In IL-6-deficient (IL-6-/-) mice, pneumonia was associated with higher lung levels of the proinflammatory cytokines tumor necrosis factor-alpha, IL-1beta, and interferon-gamma and of the antiinflammatory cytokine IL-10 than in wild type (IL-6+/+) mice (all P < .05). Also, the plasma concentrations of soluble tumor necrosis factor receptors were higher in IL-6-/- mice (P < .05), while the acute-phase protein response was strongly attenuated (P < .01). Lungs harvested from IL-6-/- mice 40 h after inoculation contained more S. pneumoniae colonies (P < .05). IL-6-/- mice died significantly earlier from pneumococcal pneumonia than did IL-6+/+ mice (P < .05). During pneumococcal pneumonia, IL-6 down-regulates the activation of the cytokine network in the lung and contributes to host defense.
authors.affiliation: Department of Surgery, Cornell University Medical College, New York, New York, USA.
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
authors.forename: C V
authors.initials: CV
authors.lastname: Keogh
authors.forename: X
authors.initials: X
authors.lastname: Guirao
authors.forename: W A
authors.initials: WA
authors.lastname: Buurman
authors.forename: M
authors.initials: M
authors.lastname: Kopf
authors.forename: S F
authors.initials: SF
authors.lastname: Lowry
mesh_terms: D000209:Acute-Phase Proteins / Q000032:analysis; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D015850:Interleukin-6 / Q000235:genetics / Q000502:physiology*; D008168:Lung / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000382:microbiology; D012333:RNA, Messenger / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D013296:Streptococcus pneumoniae / Q000302:isolation & purification
chemical_list: D000209:Acute-Phase Proteins; D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor