Effects of Carbon Monoxide Inhalation during Experimental Endotoxemia in Humans

• Published in: American journal of respiratory and critical care medicine 2005-02, Vol.171 (4), p.354-360
• Main Authors: Mayr, Florian B, Spiel, Alexander, Leitner, Judith, Marsik, Claudia, Germann, Peter, Ullrich, Roman, Wagner, Oswald, Jilma, Bernd
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adolescent; Adult; Air; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Blood coagulation. Blood cells; Blood. Blood coagulation. Reticuloendothelial system; Carbon Monoxide - administration & dosage; Carbon Monoxide - blood; Carbon Monoxide - pharmacology; Carboxyhemoglobin - analysis; Carboxyhemoglobin - drug effects; Carboxyhemoglobin - metabolism; Cross-Over Studies; Cytokines - blood; Cytokines - drug effects; Double-Blind Method; Endotoxemia - chemically induced; Endotoxemia - drug therapy; Fundamental and applied biological sciences. Psychology; General aspects, investigation methods, hemostasis, fibrinolysis; Humans; Intensive care medicine; Interleukins - blood; Lipopolysaccharides; Male; Medical sciences; Molecular and cellular biology; Pharmacology. Drug treatments; Pilot Projects; Reference Values; Reverse Transcriptase Polymerase Chain Reaction - methods; Tumor Necrosis Factor-alpha - drug effects; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200404-446OC

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.