Abstract

Interleukin 6 (IL-6) performs a prominent role during sepsis. To examine the molecular regulation of IL-6, IL-6 receptor, and signaling receptor gp130 during endotoxemia, nine healthy young volunteers received a bolus injection of lipopolysaccharide (LPS) on day 1 and saline on day 2 in a double blind, randomized, placebo-controlled trial. LPS enhanced IL-6 release 300-fold. IL-6 mRNA expression was not significantly altered in blood samples at any time after LPS infusion in vivo, while incubation of whole blood with 50 pg/ml LPS up-regulated IL-6 mRNA levels 8000- to 50,000-fold in vitro. LPS infusion increased synthesis of gp130 mRNA 5.5-fold compared to baseline at 4 h (P < 0.05), while no significant change was observed in the placebo period (P = 0.001 between groups). LPS increased the percentage of gp130 positive neutrophils gp130 700% over baseline at 8 h (P < 0.01 versus baseline and placebo). IL-6 receptor levels were not significantly altered by low-grade endotoxemia. In conclusion, endotoxemia up-regulates gp130 expression in vivo and in vitro. Quantification of IL-6 mRNA expression in circulating leukocytes is unlikely a suitable marker for monitoring of endotoxemia.