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Journal 'Cytokines & inflammation', 2003, No. 4

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Original Articles

Number 4'2003

EFFECT OF INTERLEUKIN 1 RECEPTOR ANTAGONIST ON THE DEVELOPMENT OF OXIDATIVE STRESS IN LUNGS

L.N. Danilov, E.S. Lebedeva, I.V. Dvorakovskaya, A.S. Simbirtsev, M.M. Ilcovich

The aim was to evaluate the effect of interleukin 1 receptor antagonist (IL-1Ra) on the development of inorganic dust-induced oxidative stress in rat's lungs. Dust (20 mg) and 5 min later 750 mg/kg recombinant human IL-1Ra (or 0,9 % NaCl in control rats) were instilled in lungs via trachea. Bronchoalveolar lavage fluid cytogram, alveolar macrophage (AM) oxidative and phagocytic activities were determined at the 3rd, 7th, 14th, and 30th day. AM production of reactive oxygen species (ROS) was determined by luminol-dependent chemiluminescence (CL). Histologic studies of lung tissue were performed. In control at the 3rd day after dust administration AM oxidative activity increased 4-5-fold above normal level. Neutrophil recovery increased up to 49,5 % (normal 1-2 %). IL-1Ra treatment prevented the "burst" of AM oxidative activity and decreased 3-fold neutrophil influx. We suppose this effect is associated with prevention of AMs IL-1 hyperproduction because of surface receptor blockade with IL-1Ra. As a result IL-1 proinflammatory effect is suppressed. Beginning from the 7th day CL kinetics in IL-1Ra-group didn't differ from control group but significant differences were observed in histologic lung pictures. In control group erosive bronchitis and pneumonia foci were determined in lung tissue throughout a month. In IL-1Ra-group structural changes characterized as bronchial catarrh, bronchial pneumonia was not determined, the number of dust particles was decreased in comparison with control group. It's possible that prevention of excessive ROS generation by means of IL-1Ra resulted in better preservation of lung tissue structure. If the excessive ROS generation doesn't correspond to the character and power of damage factor, IL-1Ra may be used for removal the ROS-induced injury effect. (Cytokines and inflammation, 2003, Vol. 2, № 4, p. 14-20)

Keywords: interleukin 1, interleukin 1 receptor antagonist, alveolar macrophages, reactive oxygen forms.

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