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Published ahead of print on November 19, 2004, doi:10.1164/rccm.200404-446OC
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American Journal of Respiratory and Critical Care Medicine Vol 171. pp. 354-360, (2005)
© 2005 American Thoracic Society
doi: 10.1164/rccm.200404-446OC

Original Article

Effects of Carbon Monoxide Inhalation during Experimental Endotoxemia in Humans

Florian B. Mayr, Alexander Spiel, Judith Leitner, Claudia Marsik, Peter Germann, Roman Ullrich, Oswald Wagner and Bernd Jilma

Departments of Clinical Pharmacology, Medical and Chemical Laboratory Diagnostics, and Anesthesiology and General Critical Care Medicine, Medical University of Vienna, Vienna, Austria

Correspondence and requests for reprints should be addressed to Bernd Jilma, M.D., Department of Clinical Pharmacology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria. E-mail: Bernd.Jilma{at}meduniwien.ac.at

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-1{alpha} and IL-1ß 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.

Key Words: carboxyhemoglobin • endotoxin • tumor necrosis factor-{alpha}




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