TUMOR-NECROSIS-FACTOR ACTIVITY INCREASES IN THE EARLY RESPONSE TO TRAUMA

Objectives: 1) To determine whether tumor necrosis factor (TNF) up-reg ulation occurs in the first hours following severe injury, 2) To deter mine whether the time from injury to blood sampling affects the probab ility of detecting TNF. Methods: A prospective, cross-sectional study was performed using a convenience sample of adult major trauma patient s (''patients'') treated at a university hospital ED (Level-1 trauma c enter) and 20 healthy volunteers (''controls''). The time interval fro m injury to specimen collection (Delta T), the injury severity scale ( ISS) score, patient demographics, and quantitative cytokine [TNF and i nterleukin (IL-6, IL-8)] levels were measured. In the patients, cytoki ne levels were analyzed as a function of Delta T (using first hourly c utoff points and then the median T as an arbitrary cutoff point) with and without potential confounders (e.g., ISS, age, gender), Results: T he mean Delta T was 92.8 +/- 49.2 min (range 10-210 min, median 82 min ). In the controls, TNF activity was present in 96%, with a mean level of 125 pg/mL. The controls showed no baseline IL-6 activity and only 10% had a measurable baseline IL-8 level. In the patients, TNF was pre sent in 93%, with a mean level of 628 +/- 138 pg/mL, When the patients ' specimens were divided at the median to obtain roughly equal sized g roups, more TNF levels were elevated >2.5 SD above the controls in the early vs late group (51% vs 30%; p = 0.07). The mean levels of TNF an d IL-8 also were higher in the early vs late group (756 vs 530 and 287 vs 135, respectively; p < 0.05). Conclusions: TNF levels are elevated in the immediate 4 hours post-injury. Previous investigators' inabili ty to detect TNF activity increases may be related to delays in sampli ng. These results are consistent with the theory that increased TNF ac tivity occurs early after major trauma and may initiate subsequent cyt okine activity.