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Does carbon monoxide treatment alter cytokine levels after endotoxin infusion in pigs?: A randomized controlled study
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.ORCID iD: 0000-0002-5325-2688
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Anaesthesiology.
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2008 (English)In: Journal of Inflammation, ISSN 1476-9255, Vol. 5, 13.- p.Article in journal (Refereed) Published
Abstract [en]

ABSTRACT: BACKGROUND: Carbon monoxide (CO) has recently been suggested to have anti-inflammatory properties, but data seem to be contradictory and species-specific. Thus, in studies on macrophages and mice, pretreatment with CO attenuated the inflammatory response after endotoxin exposure. On the other hand, human studies showed no effect of CO on the inflammatory response. Anti-inflammatory efficacy of CO has been shown at concentrations above 10% carboxyhaemoglobin. This study was undertaken to elucidate the possible anti-inflammatory effects of CO at lower CO concentrations. METHODS: Effects of CO administration on cytokine (TNF-alpha, IL-6, IL-1beta and IL-10) release were investigated in a porcine model in which a systemic inflammatory response syndrome was induced by endotoxin infusion. Endotoxin was infused in 20 anaesthetized and normoventilated pigs. Ten animals were targeted with inhaled CO to maintain 5% COHb, and 10 animals were controls. RESULTS: In the control group, mean pulmonary artery pressure increased from a baseline value of 17 mmHg (mean, n = 10) to 42 mmHg (mean, n = 10) following 1 hour of endotoxin infusion. Similar mean pulmonary artery pressure values were found in animals exposed to carbon monoxide. Plasma levels of all of the measured cytokines increased in response to the endotoxin infusion. The largest increase was observed in TNF-alpha, which peaked after 1.5 hours at 9398 pg/ml in the control group and at 13395 pg/ml in the carbon monoxide-exposed group. A similar peak was found for IL-10 while the IL-6 concentration was maximal after 2.5 hours. IL-1beta concentrations increased continuously during the experiment. There were no significant differences between carbon monoxide-exposed animals and controls in any of the measured cytokines. CONCLUSION: Our conclusion is that 5% COHb does not modify the cytokine response following endotoxin infusion in pigs.

Place, publisher, year, edition, pages
2008. Vol. 5, 13.- p.
URN: urn:nbn:se:umu:diva-2755DOI: 10.1186/1476-9255-5-13PubMedID: 18687112OAI: diva2:141016
Available from: 2007-11-09 Created: 2007-11-09 Last updated: 2015-09-15Bibliographically approved
In thesis
1. Carbon monoxide in biological systems: An experimental and clinical study
Open this publication in new window or tab >>Carbon monoxide in biological systems: An experimental and clinical study
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Carbon monoxide (CO) is a toxic gas, but it is also produced endogenously when haem is degraded. When produced in vivo, CO is believed to have positive biological effects. For example it activates the production of cyclic guanosine mono-phosphate and causes vasodilatation. CO is also believed to have anti-inflammatory properties by binding to Mitogen activated protein (MAP) kinase. Several studies in cells, mice and rats support this opinion regarding both the circulatory as well as the anti-inflammatory properties. However, studies in larger animals regarding circulatory effects have demonstrated contradictory results. The only study in humans regarding anti-inflammatory properties of CO could not demonstrate such effects.

Methods: This thesis consists of four different models. In paper I a method for analysis of CO in blood was developed using gas chromatography. In paper II a porcine model was used to investigate the elimination time for CO. The pigs in paper II had a high concentration of CO administered via blood, and CO concentrations were followed over time and kinetically parameters calculated. Circulatory parameters were also measured to evaluate if there were any circulatory changes after CO administration. In paper III CO´s anti-inflammatory properties were investigated in an endotoxin-induced systemic inflammatory model in pigs. Paper III was a randomized study where one group inhaled CO and the other group served as controls. Plasma cytokine concentrations were measured and followed over time as an indication of the inflammatory state. In paper IV, CO concentrations in blood from blood donors at the Blood Centre in Umeå were investigated. The blood donors also completed a questionnaire about age, smoking history and other possible sources for exogenous contamination of CO in the blood.

Results and conclusions: In paper I we developed a method suitable for analysis of low concentrations of CO in blood. The half-life of CO at levels of 250 µM in pigs was found to be 60 minutes. CO did not show anti-inflammatory effects after an endotoxin-induced systemic inflammation in pigs. In banked blood CO was present at concentrations up to six times higher than normal concentrations. This could be a risk when transfusing such blood to susceptible patients.

Place, publisher, year, edition, pages
Umeå: Kirurgisk och perioperativ vetenskap, 2007. 42 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1134
Carbon monoxide, physiological effects, systemic inflammation, analytical method, blood, exhaled air, pharmacokinetics, cigarette smoking, blood donation, cytokines
National Category
Anesthesiology and Intensive Care
urn:nbn:se:umu:diva-1427 (URN)978-91-7264-431-1 (ISBN)
Public defence
2007-11-30, Sal B, 9tr, Tandläkarhögskolan, Umeå Universitet, Umeå, 13:00 (English)
Available from: 2007-11-09 Created: 2007-11-09 Last updated: 2009-09-25Bibliographically approved

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