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


METHODS
Prospective, controlled study.


METHODS
A tertiary care pediatric oncology hospital.


METHODS
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).


METHODS
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.


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.
Schmidt
Jeffrey E
JE
Division of Critical Care Medicine, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, University of Tennessee Health Science Center, Memphis, TN, USA.
Morgan
Jim I
JI
Rodriguez-Galindo
Carlos
C
Webb
David L
DL
Liang
Hua
H
Tamburro
Robert F
RF
D000293:Adolescent; D001663:Bilirubin / Q000096:biosynthesis / Q000097:blood; D002173:Cancer Care Facilities; D002263:Carboxyhemoglobin / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D005260:Female; D006419:Heme Oxygenase (Decyclizing) / Q000097:blood* / Q000235:genetics; D051547:Heme Oxygenase-1; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins; D009369:Neoplasms / Q000097:blood / Q000150:complications; D011446:Prospective Studies; D012333:RNA, Messenger / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000150:complications
D008565:Membrane Proteins; D012333:RNA, Messenger; D002263:Carboxyhemoglobin; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001663:Bilirubin