Interieukin-10 impairs host defense in murine pneumococcal pneumonia

T van der Poll, A Marchant, CV Keogh… - Journal of Infectious …, 1996 - academic.oup.com
T van der Poll, A Marchant, CV Keogh, M Goldman, SF Lowry
Journal of Infectious Diseases, 1996academic.oup.com
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 106 cfu
of Streptococcus pneumoniae. Pneumonia induced sustained expression of IL-lO 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-α (TNF) and interferon (lFN)-γ, increased bacterial …
Abstract
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 106 cfu of Streptococcus pneumoniae. Pneumonia induced sustained expression of IL-lO 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-α (TNF) and interferon (lFN)-γ, 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-γ, 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 proinflammatorycytokine response within the lungs, hampers effective clearance of the infection, and shortens survival.
Oxford University Press