Cytokine mediation of ozone-induced pulmonary adaptation.
Previous studies have shown that a single exposure of animals to ozone (O3) can induce protection or adaptation to the acute injurious effects of a subsequent O3 challenge. Although a number of mechanisms have been proposed to account for this response, none appear to be fully explanatory. We examined the role interleukin (IL)-6 may play in the induction of adaptation to O3-induced pulmonary injury. A statistically significant 29-fold increase in bronchoalveolar lavage fluid IL-6 levels was observed in rats exposed to 0.5 ppm O3 during nighttime hours when compared with daytime hours even though similar kinetics of inflammation were induced by each exposure. Animals receiving an initial nighttime O3 exposure showed a lesser degree of inflammation following a subsequent O3 exposure when compared with animals which received an initial daytime exposure. Rats pretreated with IL-6 both intratracheally and intraperitoneally and subsequently exposed to O3 showed a lesser degree of cellular inflammation when compared with respective controls. Pretreatment of rats with anti-IL-6-receptor antibodies (ra) prior to the nighttime O3 exposure completely abrogated the O3-induced cellular adaptive response without effecting the inflammatory response induced by the initial nighttime O3 exposure. In fact, administration of anti-IL-6ra augmented the neutrophil influx following the second O3 exposure. Anti-IL-6ra treatment did not alter the pulmonary edema adaptive response, suggesting that the O3-induced cellular and edema adaptive responses are regulated by different mechanisms. Our data indicate that mobilization of pulmonary antioxidants does not play a role in the IL-6-mediated early cellular adaptive response and suggest that IL-6 is an essential mediator of the O3-induced cellular adaptive response.
McKinney
W J
WJ
Center for Environmental Medicine, University of North Carolina, Chapel Hill, USA.
Jaskot
R H
RH
Richards
J H
JH
Costa
D L
DL
Dreher
K L
KL
D000222:Adaptation, Physiological / Q000187:drug effects / Q000276:immunology*; D000397:Air Pollution; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D002940:Circadian Rhythm / Q000187:drug effects; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000494:pharmacology; D008168:Lung / Q000276:immunology*; D008297:Male; D010083:Oxidants, Photochemical / Q000494:pharmacology*; D010126:Ozone / Q000494:pharmacology*; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D019947:Receptors, Interleukin-6 / Q000276:immunology
D000906:Antibodies; D016207:Cytokines; D015850:Interleukin-6; D010083:Oxidants, Photochemical; D019947:Receptors, Interleukin-6; D010126:Ozone