Absence of endogenous interleukin-10 enhances the evolution of acute lung injury

Eur Cytokine Netw. 2002 Jul-Sep;13(3):285-97.


Interleukin-10 (IL-10) exerts a wide spectrum of regulatory activities in the immune and inflammatory response. The aim of this study was to investigate the role of endogenous IL-10 on the modulation of the inflammatory response in mice subjected to carrageenan-induced lung injury. When compared to carrageenan-treated IL-10 wild-type (WT) mice, carrageenan-treated IL-10 knock-out mice (IL-10KO) mice experienced a higher rate of pleural exudation, and polymorphonuclear cell migration. Exudate levels of the pro-inflammatory cytokines tumour necrosis factor, interleukin-1beta and interleukin-6 were also greatly enhanced in IL-10KO mice in comparison to wild-type mice. Lung myeloperoxidase (MPO) activity was significantly reduced in IL-10WT mice when compared to IL-10KO mice-treated with carrageenan. The degree of oxidative and nitrosative damage was significantly higher in IL-10KO mice than in wild-type littermates, as indicated by elevated malondialdehyde levels and formation of nitrotyrosine and poly (ADP-ribose) synthetase (PARS). Staining of lung tissue sections obtained from carrageenan-treated IL-10WT with an anti-COX-2 antibody showed a positive staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase (iNOS) was found mainly in the macrophages of the inflamed lungs from carrageenan-treated IL-10WT mice. The intensity and degree of the staining for COX-2 and iNOS were markedly enhanced in tissue sections obtained from carrageenan-treated IL-10KO mice. Most notably, the degree of lung injury caused by carrageenan was also enhanced in IL-10KO mice. Taken together, our results clearly demonstrate that endogenous IL-10 exerts an anti-inflammatory role during acute inflammation and tissue damage associated with carrageenan-induced pleurisy, possibly by regulating neutrophil recruitment, and the subsequent cytokine and oxidant generation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Carrageenan / toxicity
  • Cell Adhesion Molecules / metabolism
  • Cyclooxygenase 2
  • Cytokines / biosynthesis
  • Cytokines / metabolism
  • Enzyme Activation
  • Immunohistochemistry
  • Interleukin-10 / genetics
  • Interleukin-10 / physiology*
  • Isoenzymes / metabolism
  • Lipid Peroxidation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Peroxidase / metabolism
  • Pleurisy / chemically induced
  • Pleurisy / enzymology
  • Pleurisy / physiopathology*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Tyrosine / analogs & derivatives*
  • Tyrosine / biosynthesis


  • Cell Adhesion Molecules
  • Cytokines
  • Isoenzymes
  • Interleukin-10
  • Nitric Oxide
  • 3-nitrotyrosine
  • Tyrosine
  • Carrageenan
  • Peroxidase
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Poly(ADP-ribose) Polymerases