Numerous cytokines may contribute to the inflammation seen in hyperoxia-induced lung injury. To date, few studies have examined the effects of hyperoxia on the production of monocyte chemotactic protein (MCP). MCP is a cytokine, released by a number of cells, that attracts monocyte lineage cells which ire important in chronic inflammation. We have recently shown that hyperoxia increases the production of MCP by U937 cells. In the current study, we examined whether this increased production of MCP was related to effects of hyperoxia on MCP RNA stability. U937 cells were treated with actinomycin to halt RNA transcription, then exposed to either normoxia (21%02/5%C02) or hyperoxia (95%02/5%C02) for varying amounts of time. Total RNA at 0,2,4, and 6 hours was examined for MCP mRNA expression by Northern blot analysis. This quantitation was normalized with actin mRNA expression to account for loading differences. Results are shown in Table 1. Table 1 2 HR 4 HR 6HR NORMOXIA 64.6+/-12.8 56.2+/-11.0 49.4+/-11.2 HYPEROXIA 80.8+M4.3 61.9+/-10.0 58.9+/-11.4 (Values are expressed as % time 0 value, mean ±SEM) The half-life of MCP mRNA in thepresence of normoxia was 5.3+/-0.5 hours compared to the half-life of MCP mRNA in the presence of hyperoxia (6.58+/-0.7 hours, p<0.05). This represents a 22% increase in MCP mRNA stability in the presence of hyperoxia, We conclude that hyperoxia increases MCP production by U937 cells in part through effects on MCP RNA stability. This may be due to effects of hyperoxia on specific MCP ribonucleases.