Role of IL-6 in the pleurisy and lung injury caused by carrageenan.
In the present study we used IL-6 knockout mice (IL-6KO) to evaluate the role of IL-6 in the inflammatory response caused by injection of carrageenan into the pleural space. Compared with carrageenan-treated IL-6 wild-type (IL-6WT) mice, carrageenan-treated IL-6KO mice exhibited a reduced degree of pleural exudation and polymorphonuclear cell migration. Lung myeloperoxidase activity and lipid peroxidation were significantly reduced in IL-6KO mice compared with those in IL-6WT mice treated with carrageenan. Immunohistochemical analysis for nitrotyrosine and poly(A)DP-ribose polymerase revealed a positive staining in lungs from carrageenan-treated IL-6WT mice. No positive staining for nitrotyrosine or PARS was found in the lungs of the carrageenan-treated IL-6KO mice. Staining of lung tissue sections obtained from carrageenan-treated IL-6WT mice with an anti-cyclo-oxygenase-2 Ab showed a diffuse staining of the inflamed tissue. Furthermore, expression of inducible nitric oxide synthase was found mainly in the macrophages of the inflamed lungs from carrageenan-treated IL-6WT mice. The intensity and degree of the staining for cyclo-oxygenase-2 and inducible nitric oxide synthase were markedly reduced in tissue sections obtained from carrageenan-treated IL-6KO mice. Most notably, the degree of lung injury caused by carrageenan was also reduced in IL-6KO mice. Treatment of IL-6WT mice with anti-IL-6 (5 microg/day/mouse at 24 and 1 h before carrageenan treatment) also significantly attenuated all the above indicators of lung inflammation. Taken together, our results clearly demonstrate that IL-6KO mice are more resistant to the acute inflammation of the lung caused by carrageenan injection into the pleural space than the corresponding WT mice.
Cuzzocrea
S
S
Institute of Pharmacology, University of Messina School of Medicine, Italy. salvator@www.unime.it
Sautebin
L
L
De Sarro
G
G
Costantino
G
G
Rombolà
L
L
Mazzon
E
E
Ialenti
A
A
De Sarro
A
A
Ciliberto
G
G
Di Rosa
M
M
Caputi
A P
AP
Thiemermann
C
C
D000818:Animals; D002351:Carrageenan / Q000633:toxicity*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D004249:DNA Damage / Q000276:immunology; D015232:Dinoprostone / Q000378:metabolism; D004790:Enzyme Induction / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007975:Leukotriene B4 / Q000096:biosynthesis; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000276:immunology* / Q000473:pathology*; D008264:Macrophages / Q000201:enzymology / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase / Q000378:metabolism; D010994:Pleura / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010998:Pleurisy / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D002351:Carrageenan; D016207:Cytokines; D015232:Dinoprostone; D015850:Interleukin-6; D007975:Leukotriene B4; D008315:Malondialdehyde; D009566:Nitrates; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D009195:Peroxidase; D011065:Poly(ADP-ribose) Polymerases; D011451:Prostaglandin-Endoperoxide Synthases; D011460:Prostaglandins F; D014443:Tyrosine; D000093242:Interleukin-6 Inhibitors; C039642:peroxynitric acid; C002744:3-nitrotyrosine; C496317:Nos2 protein, mouse; C100006:prostaglandin F1