Absence of endogenous interleukin-10 enhances the evolution of acute lung injury.
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.
Cuzzocrea
Salvatore
S
Institute of Pharmacology, School of Medicine, University of Messina, Torre Biologica--Policlinico Universitario Via C. Valeria, Gazzi, 98100 Messina Italy. salvatore@www.unime.it
Mazzon
Emanuela
E
Dugo
Laura
L
Serraino
Ivana
I
Di Paola
Rosanna
R
Genovese
Tiziana
T
De Sarro
Angela
A
Caputi
Achille P
AP
D000208:Acute Disease; D000818:Animals; D002351:Carrageenan / Q000633:toxicity; D015815:Cell Adhesion Molecules / Q000378:metabolism; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004789:Enzyme Activation; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology*; D007527:Isoenzymes / Q000378:metabolism; D015227:Lipid Peroxidation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D010998:Pleurisy / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis
D015815:Cell Adhesion Molecules; D016207:Cytokines; D007527:Isoenzymes; D016753:Interleukin-10; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D002351:Carrageenan; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D011065:Poly(ADP-ribose) Polymerases