Interleukin-10 impairs host defense in murine pneumococcal pneumonia.
The effects of recombinant interleukin (IL)-10 and the role of endogenous IL-10 were determined in C57B1/6 mice with pneumonia induced by intranasal inoculation with 10(6) cfu of Streptococcus pneumoniae. Pneumonia induced sustained expression of IL-10 mRNA and protein in lungs, but IL-10 remained undetectable in plasma. Intranasal inoculation of S. pneumoniae in combination with IL-10 (1500 U/mouse) resulted in decreased lung concentrations of tumor necrosis factor-alpha (TNF) and interferon (IFN)-gamma, increased bacterial counts in lungs and blood, and early lethality. Conversely, pretreatment (-2 h) of mice with an anti-IL-10 monoclonal antibody (2 mg/mouse) was associated with increased lung levels of TNF and IFN-gamma, reduced bacterial counts in lungs and plasma 40 h after the inoculation, and prolonged survival. These results indicate that during pneumococcal pneumonia, IL-10 attenuates the proinflammatory cytokine response within the lungs, hampers effective clearance of the infection, and shortens survival.
Cornell University Medical College, Department of Surgery, New York, NY 10021, USA.
T
T
van der Poll
A
A
Marchant
C V
CV
Keogh
M
M
Goldman
S F
SF
Lowry
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D016753:Interleukin-10 / Q000494:pharmacology / Q000502:physiology*; D008168:Lung / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000302:isolation & purification
D016207:Cytokines; D011994:Recombinant Proteins; D016753:Interleukin-10