Role of IL-6 in the pleurisy and lung injury caused by carageenan

Salvatore Cuzzocrea, Lidia Sautebin, Giovambattista De Sarro, Giuseppina Costantino, Laura Rombolà, Emanuela Mazzon, Armando Ialenti, Angela De Sarro, Gennaro Ciliberto, Massimo Di Rosa, Achille P. Caputi, Christoph Thiemermann

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Abstract

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 μg/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.

Original languageEnglish
Pages (from-to)5094-5104
Number of pages11
JournalJournal of Immunology
Volume163
Issue number9
Publication statusPublished - 1999

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ASJC Scopus subject areas

  • Immunology

Cite this

Cuzzocrea, S., Sautebin, L., De Sarro, G., Costantino, G., Rombolà, L., Mazzon, E., Ialenti, A., De Sarro, A., Ciliberto, G., Di Rosa, M., Caputi, A. P., & Thiemermann, C. (1999). Role of IL-6 in the pleurisy and lung injury caused by carageenan. Journal of Immunology, 163(9), 5094-5104.