HYPEROXIA AMPLIFIES TNF-ALPHA PRODUCTION IN LPS-STIMULATED HUMAN ALVEOLAR MACROPHAGES

Human alveolar macrophages (AM) produce a number of inflammatory media tors including tumor necrosis factor (TNF). TNF-alpha has been implica ted in several forms of lung injury including that associated with oxy gen toxicity. To investigate whether oxygen could induce or augment th e release of TNF from AM, we acquired AM from nonsmoking volunteers an d determined TNF release after in vitro hyperoxia. Although TNF releas e was not induced by oxygen exposure alone, if lipopolysaccharide (LPS ) stimulation occurred simultaneously, there was significant augmentat ion by 60 and 95% oxygen over LPS-stimuiated AM exposed to 21% oxygen. This increase was paralleled by a significant increase of interleukin (IL)-1 beta. Dimethylthiourea (DMTU), a hydroxyl radical scavenger, i nhibited this release. The increase in TNF extracellular concentration s induced by hyperoxia was not associated with significant increases i n intracellular concentration or detectable mRNA over LPS-stimulated A M exposed to 21% oxygen. We hypothesize that hyperoxia exposure may al ter the LPS-stimulated AM cytoplasmic milieu, thus further enhancing T NF-alpha production by a post-transcriptional mechanism.