Effect of hyperoxia on human macrophage cytokine response

In the development of lung damage induced by oxidative stress, it has been proposed that changes in alveolar macrophages (AM) function with modifications in cytokine production may contribute to altered repair processes. To characterize the changes in profiles of cytokine production by marophages exposed to oxidants, the effects of hyperoxia (95% O-2) on interleukin (IL)-1 beta, IL-6, IL-8, and tumour necrosis factor-alpha (TNF-alpha) expression were studied. Experiments were first performed using AM obtained from control subjects and children with interstitial lung disease. Results showed that a 48 h O-2 exposure was associated with two distinct patterns of response: a decrease in TNF-alpha, IL-1 beta and IL-6 expression, and an increase in IL-8. To complete these observations we used U937 cells that were exposed for various durations to hyperoxia. We confirmed that a 48 h O-2 exposure led to similar changes with a decrease in TNF-alpha, IL-1 beta and IL-6 production and an increase in IL-8. Interestingly, this cytokine response was preceded during the first hours of O-2 treatment by induction of TNF-alpha, IL-1 beta and IL-6. These data indicate that hyperoxia induces changes in the expression of macrophages inflammatory cytokines, and that these modifications appear to be influenced by the duration of O-2 exposure.