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Heme oxygenase-1 messenger RNA expression is induced in peripheral blood mononuclear cells of pediatric cancer patients with systemic inflammatory response syndrome.

Schmidt JE, Morgan JI, Rodriguez-Galindo C, Webb DL, Liang H, Tamburro RF

Division of Critical Care Medicine, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, University of Tennessee Health Science Center, Memphis, TN, USA.

OBJECTIVE: To determine whether heme oxygenase-1 messenger RNA expression in peripheral blood mononuclear cells is induced in pediatric cancer patients with the systemic inflammatory response syndrome (SIRS) and whether this expression correlates with the heme oxygenase-1 products, bilirubin and carboxyhemoglobin. DESIGN: Prospective, controlled study. SETTING: A tertiary care pediatric oncology hospital. PATIENTS: Fourteen patients admitted to the intensive care unit with a diagnosis of SIRS by American College of Chest Physicians/Society for Critical Care Medicine consensus criteria and 17 control patients (off therapy, no acute illness). INTERVENTIONS: Blood for bilirubin, carboxyhemoglobin, and heme oxygenase-1 messenger RNA expression was collected at study entry. SIRS patients continued to have samples collected every 12 hrs for 1 wk or until intensive care unit discharge. Heme oxygenase-1, bilirubin, and carboxyhemoglobin levels of SIRS patients were compared with controls, and correlation between heme oxygenase-1 and products was assessed. MEASUREMENTS AND MAIN RESULTS: Within 48 hrs of study entry, maximum heme oxygenase-1 expression for all SIRS patients compared with controls was 5.5 +/- 1.0 vs. 1.1 +/- 0.1 (p < .0006). Maximum expression was > or =2.3-fold in 13 of 14 SIRS patients. Maximum heme oxygenase-1 expression also differed from minimum (5.5 +/- 1.0 vs. 1.6 +/- 0.3, p < .003). Maximum bilirubin and carboxyhemoglobin levels within 48 hrs of study entry differed between SIRS patients and controls (3.0 +/- 0.8 vs. 0.3 +/- 0.1, p = .006; and 1.2 +/- 0.2 vs. 0.6 +/- 0.1, p = .001, respectively). Bilirubin, but not carboxyhemoglobin, correlated with heme oxygenase-1 expression (p = .0013). CONCLUSIONS: Heme oxygenase-1 messenger RNA, bilirubin, and carboxyhemoglobin levels were increased within 48 hrs of admission in pediatric cancer patients with SIRS. Heme oxygenase-1 expression correlated with serum bilirubin levels. The increase in heme oxygenase-1 expression may add to the understanding of the increase in serum bilirubin observed in patients with SIRS/sepsis. These findings support a role for heme oxygenase-1 in the physiologic response to inflammatory stress.

Published 8 November 2004 in Pediatr Crit Care Med, 5(6): 554-60.
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