This Article Full Text Full Text (PDF) All Versions of this Article: 200404-446OCv1 171/4/354    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mayr, F. B. Articles by Jilma, B. Search for Related Content PubMed PubMed Citation Articles by Mayr, F. B. Articles by Jilma, B.

Effects of Carbon Monoxide Inhalation during Experimental Endotoxemia in Humans

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-, interleukin (IL)-6 (approximately 150-fold increases), and IL-8, as well as IL-1 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-

This article has been cited by other articles:

				L. Wang, J.-Y. S. Lee, J. H. Kwak, Y. He, S. I. Kim, and M. E. Choi Protective effects of low-dose carbon monoxide against renal fibrosis induced by unilateral ureteral obstruction Am J Physiol Renal Physiol, March 1, 2008; 294(3): F508 - F517. [Abstract] [Full Text] [PDF]

				R. Sauermann, C. Marsik, I. Steiner, K. Seir, T. Cvitko, M. Zeitlinger, O. Wagner, and C. Joukhadar Immunomodulatory Effects of Fosfomycin in Experimental Human Endotoxemia Antimicrob. Agents Chemother., May 1, 2007; 51(5): 1879 - 1881. [Abstract] [Full Text] [PDF]

				S. W. Ryter, D. Morse, and A. M. K. Choi Carbon Monoxide and Bilirubin: Potential Therapies for Pulmonary/Vascular Injury and Disease Am. J. Respir. Cell Mol. Biol., February 1, 2007; 36(2): 175 - 182. [Abstract] [Full Text] [PDF]

				E. B. Milbrandt, A. Ishizaka, and D. C. Angus Update in critical care 2005. Am. J. Respir. Crit. Care Med., April 15, 2006; 173(8): 833 - 841. [Full Text] [PDF]

				N. B. Hampson, L. K. Weaver, and C. A. Piantadosi "Low-Level" Carbon Monoxide Administration May Carry Risk Am. J. Respir. Crit. Care Med., September 15, 2005; 172(6): 784 - 784. [Full Text] [PDF]

				F. Mayr, M. Bilban, and B. Jilma "Low-Level" Carbon Monoxide Administration May Carry Risk Am. J. Respir. Crit. Care Med., September 15, 2005; 172(6): 784 - 785. [Full Text] [PDF]