Attenuation of ozone-induced lung injury by interleukin-10

Ozone (O-3), an oxidant air pollutant, is capable of producing pulmonary in flammation and injury. Exposure to O-3 results in the release of inflammato ry cytokines including tumor necrosis factor-alpha (TNF-alpha) and interleu kin-l (IL-1) by alveolar macrophages. In addition, O-3 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 inhi bits the synthesis of TNF-alpha and IL-1 by macrophages and decreases the e xpression of iNOS. To test the protective properties of IL-10 in vivo, on t he pulmonary injury induced by O-3 exposure, we intratracheally instilled r at recombinant IL-10 1 h prior to O-3 exposure (0.8 ppm x 3 h). Approximate ly 10-12 h following exposure, the animals were sacrificed acid the broncho alveolar lavage fluid (BALF) collected. The quantification of albumin, prot ein and fibronectin in the BALF provided a means of assessing pulmonary inj ury while the analysis of the BALF cells reflected the inflammatory respons e. Ozone exposure resulted in a significant (P < 0.05) increase in BALF alb umin, protein and fibronectin content as compared to air-exposed controls. In addition, significant increases in the percentage of BALF polymorphonucl ear leukocytes (PMNs) and tissue expression of fibronectin mRNA were observ ed. The intratracheal instillation of IL-10 prior to O-3 exposure resulted in a significant reduction in BALE albumin, protein and fibronectin content , and lung fibronectin mRNA as compared to O-3 exposure alone. The data sho ws that IL-10, when given intratracheally, significantly reduces the pulmon ary injury following O-3 exposure in the rat. However, since the PMNs and t he levels of albumin, protein and fibronectin in the IL-10 treated group di d not reach baseline values, we conclude that other mediators of inflammati on and injury not regulated by IL-10 also contribute to the pathophysiology of O-3-induced lung injury. (C) 1999 Elsevier Science Ireland Ltd. All rig hts reserved.