Effects of carbon monoxide inhalation during experimental endotoxemia in humans.
Data show that carbon monoxide (CO) exerts direct antiinflammatory effects in vitro and in vivo after LPS challenge in a mouse model. We hypothesized that CO may act as an antiinflammatory agent in human endotoxemia. The aim of this trial was to study the effects of CO inhalation on cytokine production during experimental human endotoxemia. The main study was a randomized, double-blinded, placebo-controlled, two-way cross-over trial in healthy volunteers. Each volunteer inhaled synthetic air (as placebo) and 500 ppm CO for 1 hour in random order with a washout period of 6 weeks and received a 2-ng/kg intravenous bolus of LPS after inhalation. Carboxyhemoglobin levels were assessed as a safety parameter. CO inhalation increased carboxyhemoglobin levels from 1.2% (95% confidence interval, 1.0 to 1.4%) to peak values of 7.0% (95% confidence interval, 6.5 to 7.7%). LPS infusion transiently increased plasma concentrations of tumor necrosis factor-alpha, interleukin (IL)-6 (approximately 150-fold increases), and IL-8, as well as IL-1alpha and IL-1beta mRNA levels (an approximately 200-fold increase). These LPS-induced changes were not influenced by CO inhalation. Inhalation of 500 ppm CO for 1 hour had no antiinflammatory effects in a systemic inflammation model in humans, as 250 ppm for 1 hour did in rodents.
Mayr
Florian B
FB
Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Spiel
Alexander
A
Leitner
Judith
J
Marsik
Claudia
C
Germann
Peter
P
Ullrich
Roman
R
Wagner
Oswald
O
Jilma
Bernd
B
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000388:Air; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D002263:Carboxyhemoglobin / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D004311:Double-Blind Method; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D007378:Interleukins / Q000097:blood; D008070:Lipopolysaccharides; D008297:Male; D010865:Pilot Projects; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007378:Interleukins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002248:Carbon Monoxide; D002263:Carboxyhemoglobin