Attenuation of ozone-induced lung injury by interleukin-10.
Ozone (O3), an oxidant air pollutant, is capable of producing pulmonary inflammation and injury. Exposure to O3 results in the release of inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) by alveolar macrophages. In addition, O3 exposure results in an increased expression of the inducible isoform of nitric oxide synthetase (iNOS). Interleukin-10 (IL-10) is an anti-inflammatory cytokine which inhibits the synthesis of TNF-alpha and IL-1 by macrophages and decreases the expression of iNOS. To test the protective properties of IL-10 in vivo, on the pulmonary injury induced by O3 exposure, we intratracheally instilled rat recombinant IL-10 1 h prior to O3 exposure (0.8 ppm x 3 h). Approximately 10-12 h following exposure, the animals were sacrificed and the bronchoalveolar lavage fluid (BALF) collected. The quantification of albumin, protein and fibronectin in the BALF provided a means of assessing pulmonary injury while the analysis of the BALF cells reflected the inflammatory response. Ozone exposure resulted in a significant (P<0.05) increase in BALF albumin, protein and fibronectin content as compared to air-exposed controls. In addition, significant increases in the percentage of BALF polymorphonuclear leukocytes (PMNs) and tissue expression of fibronectin mRNA were observed. The intratracheal instillation of IL-10 prior to O3 exposure resulted in a significant reduction in BALF albumin, protein and fibronectin content, and lung fibronectin mRNA as compared to O3 exposure alone. The data shows that IL-10, when given intratracheally, significantly reduces the pulmonary injury following O3 exposure in the rat. However, since the PMNs and the levels of albumin, protein and fibronectin in the IL-10 treated group did not reach baseline values, we conclude that other mediators of inflammation and injury not regulated by IL-10 also contribute to the pathophysiology of O3-induced lung injury.
Reinhart
P G
PG
Department of Occupational and Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USA.
Gupta
S K
SK
Bhalla
D K
DK
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D005353:Fibronectins / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology / Q000502:physiology*; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D020556:Neutrophil Infiltration; D010083:Oxidants, Photochemical / Q000008:administration & dosage / Q000633:toxicity*; D010126:Ozone / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology
D000418:Albumins; D005353:Fibronectins; D010083:Oxidants, Photochemical; D011506:Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016753:Interleukin-10; D010126:Ozone