PMID- 28650775 OWN - NLM STAT- MEDLINE DCOM- 20170919 LR - 20180103 IS - 1938-5404 (Electronic) IS - 0033-7587 (Linking) VI - 188 IP - 3 DP - 2017 Sep TI - Urine Interleukin-18 (IL-18) as a Biomarker of Total-Body Irradiation: A Preliminary Study in Nonhuman Primates. PG - 325-334 LID - 10.1667/RR14768.1 [doi] AB - We have reported that circulating IL-18 can be used as a radiation biomarker in mice, minipigs and nonhuman primates (NHPs, Macaca mulatta). Here, we report the levels of IL-18 in individual NHP's urine before and at 6 h-7 days after 5.0, 6.5 and 8.5 Gy (60)Co total-body irradiation (TBI) using enzyme linked immunosorbent assay (ELISA). Six animals (3.5-5.5 kg, 3-4 years old) per radiation dose were investigated. Correlation values between urine IL-18 and blood cell counts and serum chemistry parameters including lactate dehydrogenase (LDH), lipase, and serum total protein (TP), as well as between urine IL-18 and 60-day survival, were analyzed. Our data, to the best of our knowledge, for the first time, demonstrate that concentrations of urine IL-18 from irradiated NHPs were increased in a radiation dose-dependent manner compared to pre-TBI levels in samples from these animal (N = 18, 11.02 +/- 1.3 pg/ml). A 5.0 Gy low dose of radiation ( approximately LD(10/60)) did not increase urine IL-18 levels. In contrast, high-dose TBI significantly increased urine IL-18 at day 1 to day 5 in a bell-shaped time course, reaching a peak of 5- to 10-fold of control levels on day 3 after 6.5 Gy ( approximately LD(50/60)) and 8.5 Gy ( approximately LD(90/60)), respectively. Statistical analysis using receiver operator characteristic (ROC) and MultiROC analysis indicated that white blood cell and platelet counts, serum LDH, lipase and TP, when combined with urine IL-18, provide discriminatory predictors of total-body radiation injury with a very high ROC area of 0.98. Urine IL-18 measurement, as an early prognostic indicator of survival, may facilitate rapid detection of lethal doses of radiation, based on the currently available data set. FAU - Xiao, Mang AU - Xiao M AD - a Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland. FAU - Bolduc, David L AU - Bolduc DL AD - a Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland. FAU - Li, XiangHong AU - Li X AD - a Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland. FAU - Cui, Wanchang AU - Cui W AD - a Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland. FAU - Hieber, Kevin P AU - Hieber KP AD - a Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland. FAU - Bunger, Rolf AU - Bunger R AD - b Consultant, McLean, Virginia. FAU - Ossetrova, Natalia I AU - Ossetrova NI AD - a Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, Bethesda, Maryland. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170626 PL - United States TA - Radiat Res JT - Radiation research JID - 0401245 RN - 0 (Biomarkers) RN - 0 (Interleukin-18) SB - IM MH - Animals MH - Biological Assay/*methods MH - Biomarkers/urine MH - Dose-Response Relationship, Radiation MH - Female MH - Humans MH - Interleukin-18/*urine MH - Macaca mulatta MH - Male MH - Pilot Projects MH - Radiation Dosage MH - Radiation Exposure/*analysis MH - Reproducibility of Results MH - Sensitivity and Specificity MH - Whole-Body Counting/*methods EDAT- 2017/06/27 06:00 MHDA- 2017/09/20 06:00 CRDT- 2017/06/27 06:00 PHST- 2017/06/27 06:00 [pubmed] PHST- 2017/09/20 06:00 [medline] PHST- 2017/06/27 06:00 [entrez] AID - 10.1667/RR14768.1 [doi] PST - ppublish SO - Radiat Res. 2017 Sep;188(3):325-334. doi: 10.1667/RR14768.1. Epub 2017 Jun 26.