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Beneficial effects of the heme oxygenase-1/carbon monoxide system

Introduction

It has been reported that the blood level of carboxyhemoglobin (CO-Hb) is increased in critically ill patients such as those with sepsis or multiple trauma [1, 2]. Because carbon monoxide (CO) is one of the metabolites of heme catabolism, it has been suggested that there may be increased breakdown of heme in these patients. Heme oxygenase (HO) is the enzyme involved in the rate-limiting step for catabolism of heme-containing proteins. It was recently reported that HO-1 acts as a potent anti-inflammatory agent and antioxidant through its products [3]. HO-1 may therefore be an inducible defense against cellular stress that occurs during the inflammatory process [1, 4]. Against this background, we decided to evaluate the relation among the blood level of CO, HO-1 expression by monocytes, oxidative stress, and the outcome of sepsis.

Methods

Thirty patients who fulfilled the criteria for severe sepsis or septic shock and 17 other patients without sepsis during their stay in the ICU were studied. HO-1 expression by monocytes, arterial CO, oxidative stress, and cytokines were measured.

Results

Arterial blood levels of CO, cytokines, as well as monocyte HO-1 expression were higher in septic shock patients than in nonseptic patients. Increased HO-1 expression was significantly correlated with the arterial CO concentration and oxidative stress. There was a positive correlation between survival and higher HO-1 expression or CO level.

Conclusion

We found that the increase of endogenous CO production in sepsis mainly reflects increased heme turnover secondary to upregulation of HO-1, which is partially in response to systemic oxidative stress. A strong correlation between the blood CO level and survival supports the beneficial effect of HO-1 upregulation and increased CO production in patients with sepsis.

References

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    Hoetzel A, et al.: Carbon monoxide in sepsis. Antioxid Redox Signal 2007, 9: 2013-2026. 10.1089/ars.2007.1762

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    Bauer M, et al.: The heme oxygenase–carbon monoxide system: regulation and role in stress response and organ failure. Intensive Care Med 2008, 34: 640-648. 10.1007/s00134-008-1010-2

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    Foresti R, et al.: Use of carbon monoxide as a therapeutic agent: promises and challenges. Intensive Care Med 2008, 34: 649-658. 10.1007/s00134-008-1011-1

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    Scott JR, et al.: Restoring homeostasis: is heme oxygenase-1 ready for the clinic? Trends Pharmacol Sci 2007, 28: 200-205. 10.1016/j.tips.2007.03.006

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Takeyama, N., Takaki, S., Kajita, Y. et al. Beneficial effects of the heme oxygenase-1/carbon monoxide system. Crit Care 13, P367 (2009). https://doi.org/10.1186/cc7531

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Keywords

  • Septic Shock
  • Severe Sepsis
  • Blood Level
  • Heme Oxygenase
  • Multiple Trauma