Xanthine oxidase activity and blood glutathione redox ratio in infants andchildren with septic shock syndrome

Objectives: The possible role of xanthine oxidase (XO) activation in the si gnal transduction process during the septic shock syndrome was examined. Th e XO activity index after caffeine intake was assessed simultaneously with the blood glutathione redox ratio, a known parameter of oxidative stress. Design and setting: An investigational clinical study in a nine-bed pediatr ic intensive care unit. Patients: Critically ill infants and children (n = 34) with systemic inflam matory response syndrome following infection, trauma or major surgery. Bioc hemical investigations (n = 54) were performed at various stages of the sho ck syndrome, characterized by pediatric risk of mortality and organ dysmeta bolic scores. Controls consisted of 30 healthy children. Measurements and results: The in vivo XO activity index was measured as the urinary ratio of two metabolites of caffeine: 1-methyluric acid and 1-meth ylxanthine. The blood concentrations of oxidized (GSSG) and reduced glutath ione (GSH) were determined. The XO activity index and redox ratio GSSG/GSH were highly increased in patients in shock dominated by the clinical sympto ms of a proinflammatory response. A significantly lower XO activity index w as found with an increased GSSG/GSH in patients whose stage of shock was ch aracteristic of an excessive anti-inflammatory response. The XO activity in dex and GSSG/GSH were correlated closely with each other (r = 0.624, n = 54 ; p < 0.001), and were also related to the daily severity scores. Conclusion: Potent and simultaneous activation of the two redox systems str ongly indicates a definite role of free radicals from XO in the overspill o f the acute proinflammatory reaction of the shock syndrome, followed by a s ignificant downregulation.