Tumor Necrosis Factor Activity Increases in the Early Response to Trauma

Objectives: 1) To determine whether tumor necrosis factor (TNF) up-regulation occurs in the first hours following severe injury. 2) To determine whether the time from injury to blood sampling affects the probability of detecting TNF. Methods: A prospective, cross-sectional study was performed using a convenience sample of adult major trauma patients (“patients”) treated at a university hospital ED (Level-1 trauma center) and 20 healthy volunteers (“controls”). The time interval from injury to specimen collection (ΔT), the injury severity scale (ISS) score, patient demographics, and quantitative cytokine [TNF and interleukin (IL-6, IL-8)] levels were measured. In the patients, cytokine levels were analyzed as a function of ΔT (using first hourly cutoff points and then the median T as an arbitrary cutoff point) with and without potential confounders (e.g., ISS, age, gender). Results: The mean ΔT 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 present 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 groups, 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 and 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' inability to detect TNF activity increases may be related to delays in sampling. These results are consistent with the theory that increased TNF activity occurs early after major trauma and may initiate subsequent cytokine activity.