Interleukin-6 gene-deficient mice show impaired defense against pneumococcal pneumonia.
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.
van der Poll
T
T
Department of Surgery, Cornell University Medical College, New York, New York, USA.
Keogh
C V
CV
Guirao
X
X
Buurman
W A
WA
Kopf
M
M
Lowry
S F
SF
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
D000209:Acute-Phase Proteins; D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor