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.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Prabath G
authors.initials: PG
authors.lastname: Biju
authors.forename: Sarita
authors.initials: S
authors.lastname: Garg
authors.forename: Wenze
authors.initials: W
authors.lastname: Wang
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Kovacs
authors.forename: Louis M
authors.initials: LM
authors.lastname: Fink
authors.forename: Martin
authors.initials: M
authors.lastname: Hauer-Jensen
mesh_terms: D000209:Acute-Phase Proteins; D000818:Animals; D016470:Bacteremia / Q000175:diagnosis*; D058491:Bacterial Load / Q000528:radiation effects; D018988:Bacterial Translocation / Q000528:radiation effects; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D002352:Carrier Proteins / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005453:Fluorescence; D007413:Intestinal Mucosa / Q000528:radiation effects; D008070:Lipopolysaccharides / Q000097:blood; D008099:Liver / Q000382:microbiology; D008107:Liver Diseases / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability / Q000528:radiation effects; D011498:Protein Precursors / Q000097:blood*; D012372:ROC Curve; D011833:Radiation Injuries, Experimental / Q000175:diagnosis*; D014916:Whole-Body Irradiation / Q000009:adverse effects*; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide; D002352:Carrier Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011498:Protein Precursors; D000099231:Lipopolysaccharide-Binding Protein; C000606589:CALCA protein, human; C000606590:Calca protein, mouse