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 ro le of IL-6 in the inflammatory response caused by injection of carrageenan into the pleural space. Compared with carrageenan-treated IL-6 wild-type (I L-6WT) mice, carrageenan-treated IL-6KO mice exhibited a reduced degree of pleural exudation and polymorphonuclear cell migration. Lung myeloperoxidas e activity and lipid peroxidation were significantly reduced in IL-6KO mice compared with those in IL-6WT mice treated with carrageenan. Immunohistoch emical analysis for nitrotyrosine and poly(A)DP-ribose polymerase revealed a positive staining in lungs from carrageenan-treated IL-6WT mice. No posit ive staining for nitrotyrosine or PARS was found in the lungs of the carrag eenan-treated IL-6KO mice. Staining of lung tissue sections obtained from c arrageenan-treated IL-6WT mice with an anti-cyclo-oxygenase-2 Ab showed a d iffuse staining of the inflamed tissue. Furthermore, expression of inducibl e nitric oxide synthase was found mainly in the macrophages of the inflamed lungs from carrageenan-treated IL-6WT mice. The intensity and degree of th e staining for cyclo-oxygenase-2 and inducible nitric oxide synthase were m arkedly reduced in tissue sections obtained from carrageenan-treated IL-6KO mice. Most notably, the degree of lung injury caused by carrageenan was al so reduced in IL-6KO mice. Treatment of IL-6WT mice with anti-IL-6 (5 mu g/ day/mouse at 24 and 1 h before carrageenan treatment) also significantly at tenuated all the above indicators of lung inflammation. Taken together, our results clearly demonstrate that IL-6KO mice are more resistant to the acu te inflammation of the lung caused by carrageenan injection into the pleura l space than the corresponding WT mice.