Does carbon monoxide treatment alter cytokine levels after endotoxin infusion in pigs? A randomized controlled study
Tóm tắt
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. 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. 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. Our conclusion is that 5% COHb does not modify the cytokine response following endotoxin infusion in pigs.
Tài liệu tham khảo
Motterlini R, Gonzales A, Foresti R, Clark JE, Green CJ, Winslow RM: Heme oxygenase-1-derived carbon monoxide contributes to the suppression of acute hypertensive responses in vivo. Circ Res. 1998, 83 (5): 568-577.
Suematsu M, Goda N, Sano T, Kashiwagi S, Egawa T, Shinoda Y, Ishimura Y: Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver. J Clin Invest. 1995, 96 (5): 2431-2437. 10.1172/JCI118300.
Nakao A, Kimizuka K, Stolz DB, Seda Neto J, Kaizu T, Choi AM, Uchiyama T, Zuckerbraun BS, Bauer AJ, Nalesnik MA, Otterbein LE, Geller DA, Murase N: Protective effect of carbon monoxide inhalation for cold-preserved small intestinal grafts. Surgery. 2003, 134 (2): 285-292. 10.1067/msy.2003.238.
Otterbein LE, Otterbein SL, Ifedigbo E, Liu F, Morse DE, Fearns C, Ulevitch RJ, Knickelbein R, Flavell RA, Choi AM: MKK3 mitogen-activated protein kinase pathway mediates carbon monoxide-induced protection against oxidant-induced lung injury. Am J Pathol. 2003, 163 (6): 2555-2563.
Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk M, Davis RJ, Flavell RA, Choi AM: Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med. 2000, 6 (4): 422-428. 10.1038/74680.
Zuckerbraun BS, McCloskey CA, Gallo D, Liu F, Ifedigbo E, Otterbein LE, Billiar TR: Carbon monoxide prevents multiple organ injury in a model of hemorrhagic shock and resuscitation. Shock. 2005, 23 (6): 527-532.
Hoetzel A, Dolinay T, Schmidt R, Choi AM, Ryter SW: Carbon monoxide in sepsis. Antioxid Redox Signal. 2007, 9 (11): 2013-2026. 10.1089/ars.2007.1762.
Mayr FB, Spiel A, Leitner J, Marsik C, Germann P, Ullrich R, Wagner O, Jilma B: Effects of carbon monoxide inhalation during experimental endotoxemia in humans. Am J Respir Crit Care Med. 2005, 171 (4): 354-360. 10.1164/rccm.200404-446OC.
Aberg AM, Hultin M, Abrahamsson P, Larsson JE: Circulatory effects and kinetics following acute administration of carbon monoxide in a porcine model. Life Sci. 2004, 75 (9): 1029-1039. 10.1016/j.lfs.2003.12.030.
Sundin AM, Larsson JE: Rapid and sensitive method for the analysis of carbon monoxide in blood using gas chromatography with flame ionisation detection. Journal of chromatography. 2002, 766 (1): 115-121. 10.1016/S0378-4347(01)00460-1.
Mazzola S, Forni M, Albertini M, Bacci ML, Zannoni A, Gentilini F, Lavitrano M, Bach FH, Otterbein LE, Clement MG: Carbon monoxide pretreatment prevents respiratory derangement and ameliorates hyperacute endotoxic shock in pigs. Faseb J. 2005, 19 (14): 2045-2047.
Tuchscherer M, Kanitz E, Puppe B, Tuchscherer A, Stabenow B: Effects of postnatal social isolation on hormonal and immune responses of pigs to an acute endotoxin challenge. Physiol Behav. 2004, 82 (2-3): 503-511. 10.1016/j.physbeh.2004.04.056.
Brix-Christensen V, Gjedsted J, Andersen SK, Vestergaard C, Nielsen J, Rix T, Nyboe R, Andersen NT, Larsson A, Schmitz O, Tonnesen E: Inflammatory response during hyperglycemia and hyperinsulinemia in a porcine endotoxemic model: the contribution of essential organs. Acta Anaesthesiol Scand. 2005, 49 (7): 991-998. 10.1111/j.1399-6576.2005.00749.x.
Myers MJ, Farrell DE, Palmer DC, Post LO: Inflammatory mediator production in swine following endotoxin challenge with or without co-administration of dexamethasone. Int Immunopharmacol. 2003, 3 (4): 571-579. 10.1016/S1567-5769(03)00048-1.
Goldfarb RD, Dellinger RP, Parrillo JE: Porcine models of severe sepsis: emphasis on porcine peritonitis. Shock. 2005, 24 Suppl 1: 75-81. 10.1097/01.shk.0000191337.01036.b7.
Swindle MM, Smith AC, Hepburn BJ: Swine as models in experimental surgery. J Invest Surg. 1988, 1 (1): 65-79. 10.3109/08941938809141077.
Konrad D, Haney M, Johansson G, Wanecek M, Weitzberg E, Oldner A: Cardiac effects of endothelin receptor antagonism in endotoxemic pigs. American journal of physiology. 2007, 293 (2): H988-96.
Frank JW, Carroll JA, Allee GL, Zannelli ME: The effects of thermal environment and spray-dried plasma on the acute-phase response of pigs challenged with lipopolysaccharide. J Anim Sci. 2003, 81 (5): 1166-1176.
Bergmann M, Gornikiewicz A, Tamandl D, Exner R, Roth E, Fugger R, Gotzinger P, Sautner T: Continuous therapeutic epinephrine but not norepinephrine prolongs splanchnic IL-6 production in porcine endotoxic shock. Shock. 2003, 20 (6): 575-581. 10.1097/01.shk.0000095934.86703.83.
Javeshghani D, Magder S: Regional changes in constitutive nitric oxide synthase and the hemodynamic consequences of its inhibition in lipopolysaccharide-treated pigs. Shock. 2001, 16 (3): 232-238.
Nalos M, Vassilev D, Pittner A, Asfar P, Bruckner UB, Schneider EM, Georgieff M, Radermacher P, Froeba G: Tin-mesoporphyrin for inhibition of heme oxygenase during long-term hyperdynamic porcine endotoxemia. Shock. 2003, 19 (6): 526-532. 10.1097/01.shk.0000070732.34700.07.
Kondo A, Saito Y, Seki A, Sugiura C, Maegaki Y, Nakayama Y, Yagi K, Ohno K: Delayed neuropsychiatric syndrome in a child following carbon monoxide poisoning. Brain Dev. 2007, 29 (3): 174-177. 10.1016/j.braindev.2006.08.002.
Mannaioni PF, Vannacci A, Masini E: Carbon monoxide: the bad and the good side of the coin, from neuronal death to anti-inflammatory activity. Inflamm Res. 2006, 55 (7): 261-273. 10.1007/s00011-006-0084-y.
Ekblom B, Huot R: Response to submaximal and maximal exercise at different levels of carboxyhemoglobin. Acta Physiol Scand. 1972, 86 (4): 474-482.
Anderson EW, Andelman RJ, Strauch JM, Fortuin NJ, Knelson JH: Effect of low-level carbon monoxide exposure on onset and duration of angina pectoris. A study in ten patients with ischemic heart disease. Ann Intern Med. 1973, 79 (1): 46-50.
Aronow WS, Isbell MW: Carbon monoxide effect on exercise-induced angina pectoris. Ann Intern Med. 1973, 79 (3): 392-395.
Aronow WS, Stemmer EA, Isbell MW: Effect of carbon monoxide exposure on intermittent claudication. Circulation. 1974, 49 (3): 415-417.
Aronow WS: Aggravation of angina pectoris by two percent carboxyhemoglobin. Am Heart J. 1981, 101 (2): 154-157. 10.1016/0002-8703(81)90658-X.
Klimisch HJ, Chevalier HJ, Harke HP, Dontenwill W: Uptake of carbon monoxide in blood of miniture pigs and other mammals. Toxicology. 1975, 3 (3): 301-310. 10.1016/0300-483X(75)90031-1.
Westphal M, Weber TP, Meyer J, von Kegler S, Van Aken H, Booke M: Affinity of carbon monoxide to hemoglobin increases at low oxygen fractions. Biochem Biophys Res Commun. 2002, 295 (4): 975-977. 10.1016/S0006-291X(02)00781-7.