PT - JOURNAL ARTICLE AU - Jinman Cai AU - Todd McKinley AU - Isabel Billiar AU - Mazen S Zenati AU - Greg Gaski AU - Yoram Vodovotz AU - Danielle S Gruen AU - Timothy R Billiar AU - Rami A Namas TI - Protective/reparative cytokines are suppressed at high injury severity in human trauma AID - 10.1136/tsaco-2020-000619 DP - 2021 Mar 01 TA - Trauma Surgery & Acute Care Open PG - e000619 VI - 6 IP - 1 4099 - http://tsaco.bmj.com/content/6/1/e000619.short 4100 - http://tsaco.bmj.com/content/6/1/e000619.full SO - Trauma Surg Acute Care Open2021 Mar 01; 6 AB - Background Trauma elicits a complex inflammatory response that, among multiple presenting factors, is greatly impacted by the magnitude of injury severity. Herein, we compared the changes in circulating levels of mediators with known proinflammatory roles to those with known protective/reparative actions as a function of injury severity in injured humans.Methods Clinical and biobank data were obtained from 472 (trauma database-1 (TD-1), University of Pittsburgh) and 89 (trauma database-2 (TD-2), Indiana University) trauma patients admitted to the intensive care unit (ICU) and who survived to discharge. Injury severity was estimated based on the Injury Severity Score (ISS), and this was used as both a continuous variable and for the purpose of grouping patients into severity-based cohorts. Samples within the first 24 hours were obtained from all patients and then daily up to day 7 postinjury in TD-1. Sixteen cytokines were assayed using Luminex and were analyzed using two-way analysis of variance (p<0.05).Results Patients with higher ISSs had longer ICU and hospital stays, days on mechanical ventilation and higher rates of nosocomial infection when compared with the mild and moderate groups. Time course analysis and correlations with ISS showed that 11 inflammatory mediators correlated positively with injury severity, consistent with previous reports. However, five mediators (interleukin (IL)-9, IL-21, IL-22, IL-23 and IL-17E/25) were suppressed in patients with high ISS and inversely correlated with ISS.Discussion These findings suggest that severe injury is associated with a suppression of a subset of cytokines known to be involved in tissue protection and regeneration (IL-9, IL-22 and IL-17E/25) and lymphocyte differentiation (IL-21 and IL-23), which in turn correlates with adverse clinical outcomes. Thus, patterns of proinflammatory versus protective/reparative mediators diverge with increasing ISS.