The interval between a septic stimulus and hypoxia/reoxygenation affects cytokine elaboration by murine peritoneal macrophages.

The critically ill patient is commonly exposed to various physiological insults. The authors have previously shown that in vivo hypoxia/reoxygenation (H/R) alters the pattern of cytokines elaborated by murine peritoneal macrophages given a septic stimulus. In this study they sought to determine whether the interval between a septic stimulus and H/R affected the release of inflammatory mediators by macrophages. Adult CBA-strain mice were injected intraperitoneally with 10 micrograms of lipopolysaccharide (LPS). On day 0, 1, 2, 3, 4, or 5 after LPS injection, animals were exposed to 16 hours of hypoxia followed by 2 hours of reoxygenation. Harvested peritoneal macrophages were restimulated in vitro with 2.5 micrograms/mL LPS or left unstimulated. Culture supernatants collected at 2, 4, 6, 8, 10, and 12 hours after LPS injection were assayed for tumor necrosis factor (TNF), prostaglandin E2 (PGE2), and nitric oxide (NO) production. Macrophage-derived mediator production peaked when H/R occurred 3 days following LPS injection (P < .05). These data suggest that the interval between sepsis and subsequent H/R influences the pattern of cytokines elaborated by peritoneal macrophages given a septic stimulus.