Procalcitonin as a predictive biomarker for total body irradiation-induced bacterial load and lethality in mice Journal Article


Authors: Biju, P. G.; Garg, S.; Wang, W.; Choudhry, M. A.; Kovacs, E. J.; Fink, L. M.; Hauer-Jensen, M.
Article Title: Procalcitonin as a predictive biomarker for total body irradiation-induced bacterial load and lethality in mice
Abstract: Sepsis is the leading cause of mortality in intensive care units. Early detection and intervention are critical to prevent death. The acute radiation syndrome is characterized by damage of the gastrointestinal and hematopoietic systems. Translocation of intestinal microflora combined with immune system compromise may lead to septicemia and death. This work examined the utility of procalcitonin, a clinical sepsis biomarker, in a mouse model of radiation toxicity. C57/BL6 mice were exposed to total body irradiation (TBI). Intestinal mucosal permeability was measured in vivo, and liver bacterial load and plasma levels of procalcitonin (PCT), lipopolysaccharide (LPS), and LPS-binding protein were measured at baseline and at 3.5, 7, and 10 days after TBI. The value of early PCT in predicting subsequent lethality was determined by receiver operating characteristic analysis. Four days after TBI, a dose-dependent increase in permeability of the intestinal mucosa was observed, whereas bacterial translocation was present from day 7 onward. There was a high positive correlation between bacterial translocation and all sepsis biomarkers, with PCT exhibiting the strongest correlation. Moreover, plasma PCT levels were elevated already from day 3.5 onward, whereas LPS was elevated from day 7 and LPS-binding protein only 10 days after TBI. Receiver operating characteristic analysis revealed that PCT levels measured 3.5 days after TBI predicted lethality at 10 days. These data demonstrate the value of PCT as an early biomarker in radiation-induced bacteremia for mouse studies and suggest that clinical results from other septic conditions may apply to postradiation septicemia in humans.
Journal Title: Shock
Volume: 38
Issue: 2
ISSN: 1540-0514; 1073-2322
Publisher: Unknown  
Journal Place: United States
Date Published: 2012
Start Page: 170
End Page: 176
Language: eng
DOI/URL:
Notes: LR: 20130416; GR: R01 AA015731/AA/NIAAA NIH HHS/United States; GR: R33 AI080528/AI/NIAID NIH HHS/United States; GR: R33 AI080528/AI/NIAID NIH HHS/United States; GR: U19 AI067798/AI/NIAID NIH HHS/United States; GR: U19 AI67798/AI/NIAID NIH HHS/United States; JID: 9421564; 0 (Acute-Phase Proteins); 0 (Biological Markers); 0 (Carrier Proteins); 0 (Lipopolysaccharides); 0 (Membrane Glycoproteins); 0 (Protein Precursors); 0 (lipopolysaccharide-binding protein); 56645-65-9 (procalcitonin); 9007-12-9 (Calcitonin); NIHMS386015; OID: NLM: NIHMS386015 [Available on 08/01/13]; OID: NLM: PMC3399035 [Available on 08/01/13]; PMCR: 2013/08/01 00:00; ppublish