DIFFERENTIAL EXPRESSION OF TUMOR-NECROSIS-FACTOR AND INTERLEUKIN-6 BYPERITONEAL-MACROPHAGES IN-VIVO AND IN CULTURE

To investigate the differences in cytokine regulation in vitro as comp ared to in vivo, we examined the synthesis of tumor necrosis factor-al pha (TNF-alpha) and interleukin-6 (IL-6) by peritoneal macrophages in response to lipopolysaccharide (LPS). Mice (CBA/J) were primed with an intraperitoneal injection of complete Freund's adjuvant and after 2 w eeks, peritoneal cells were harvested for culture or mice were injecte d intraperitoneally with LPS for in vivo studies. In ascites fluid, TN F-alpha peaked 1 hour after LPS and returned to baseline levels by 4 h ours. In contrast, TNF-alpha in the media reached maximum at 7 hours. Expression of TNF-alpha messenger (m)RNA in vivo was rapid but transie nt, as levels peaked at 15 minutes and returned to baseline 1 hour aft er LPS. In contrast, TNF-alpha mRNA in vitro became maximal at 1 hour, but remained elevated to 5 hours after LPS. In vivo, IL-6 in ascites fluid peaked at 2 hours, whereas in vitro, IL-6 continued increasing t o 24 hours. In vivo, IL-6 mRNA reached maximum at 30 minutes, but fell below baseline by 1.5 hours after LPS. In contrast, IL-6 mRNA in vitr o was sustained at maximal expression between 5 to 9 hours after LPS. These results demonstrate that both TNF-alpha and IL-6 synthesis is mo re rapid in vivo than in vitro. ne rapid kinetics of cytokine expressi on in vivo must considered when designing strategies to inhibit cytoki ne action in vivo.