Endotoxemia enhances expression of the signaling receptor (GP130) on protein and molecular level.
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.
Marsik
Claudia
C
Department of Clinical Pharmacology, Division of Hematology and Immunology, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Wien, Austria, Europe.
Halama
Thomas
T
Cardona
Francesco
F
Schlifke
Irene
I
Mittermayer
Friedrich
F
Jilma
Bernd
B
D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D002452:Cell Count; D050822:Cytokine Receptor gp130; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D007962:Leukocytes; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D009000:Monocytes / Q000378:metabolism; D009504:Neutrophils / Q000378:metabolism; D012333:RNA, Messenger / Q000097:blood; D019947:Receptors, Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D013997:Time Factors
D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130