Wj. Mckinney et al., CYTOKINE MEDIATION OF OZONE-INDUCED PULMONARY ADAPTATION, American journal of respiratory cell and molecular biology, 18(5), 1998, pp. 696-705
Previous studies have shown that a single exposure of animals to ozone
(O-3) can induce protection or adaptation to the acute injurious effe
cts of a subsequent O-3 challenge. Although a number of mechanisms hav
e been proposed to account for this response, none appear to be fully
explanatory, We examined the role interleukin (IL)-6 may play in the i
nduction of adaptation to O-3-induced pulmonary injury. A statisticall
y significant 29-fold increase in bronchoalveolar lavage fluid IL-6 le
vels was observed in rats exposed to 0.5 ppm O-3 during nighttime hour
s when compared with daytime hours even though similar kinetics of inf
lammation were induced by each exposure. Animals receiving an initial
nighttime O-3 exposure showed a lesser degree of inflammation followin
g a subsequent O-3 exposure when compared with animals which received
an initial daytime exposure. Rats pretreated with IL-6 both intratrach
eally and intraperitoneally and subsequently exposed to O-3 showed a l
esser degree of cellular inflammation when compared with respective co
ntrols. Pretreatment of rats with anti-IL-6-receptor antibodies (ra) p
rior to the nighttime O-3 exposure completely abrogated the O-3-induce
d cellular adaptive response without effecting the inflammatory respon
se induced by the initial nighttime O-3 exposure. In fact, administrat
ion of anti-IL-6ra augmented the neutrophil influx following the secon
d O-3 exposure. Anti-IL-6ra treatment did not alter the pulmonary edem
a adaptive response? suggesting that the O-3-induced cellular and edem
a adaptive responses are regulated by different mechanisms. Our data i
ndicate that mobilization of pulmonary antioxidants does not play a ro
le in the IL-6-mediated early cellular adaptive response and suggest t
hat IL-6 is an essential mediator of the O-3-induced cellular adaptive
response.