Patterns of cytokine evolution (tumor necrosis factor-alpha and interleukin-6) after septic shock, hemorrhagic shock, and severe trauma

OBJECTIVE: To compare the patterns of evolution of two proinflammatory cytokines (tumor necrosis factor TNF-alpha and interleukin-6 IL-6) in two major clinical entities associated with systemic inflammatory response: septic shock and multiple trauma (with and without hemorrhagic shock). DESIGN: Prospective study of two cohorts of patients. SETTING: Critical care unit and Emergency Center of a university hospital. PATIENTS: Twenty-five nontrauma patients with septic shock and 60 multiple trauma patients (of whom eight patients were resuscitated from hemorrhagic shock). INTERVENTIONS: Serial blood samples were collected in each patient for determination of serum cytokine concentrations. Samples were obtained over 7 days in septic shock patients and 11 days in trauma patients. Standard resuscitation techniques were used in each patient. Clinical and laboratory data were prospectively collected. MEASUREMENTS AND MAIN RESULTS: High concentrations of circulating TNF-alpha and IL-6 were found in patients with septic shock. High IL-6 concentrations, but normal TNF-alpha concentrations were detected in trauma patients. At study entry, TNF-alpha concentrations were higher in nonsurvivor septic shock than in nonsurvivor trauma patients (42 +/- 7 vs 13 +/- 2 pg/mL; p < .001). During the whole study period, nonsurvivor septic shock patients maintained higher TNF-alpha concentrations than nonsurvivor trauma patients (p < .001). In survivors in both groups, normal values for TNF-alpha were detected during the whole study period. At study entry, IL-6 concentrations were significantly higher in nonsurvivor septic shock patients than in nonsurvivor trauma patients (15,627 +/- 4336 vs. 317 +/- 124 pg/mL; p < .0001). During the whole study period, much higher concentrations of IL-6 were detected in septic shock patients than in trauma patients (p < .0001). In survivors, at study entry, IL-6 concentrations were much higher in septic shock patients than in trauma patients (3947 +/- 1410 vs. 247 +/- 41 pg/mL; p < .001). Higher IL-6 concentrations were maintained throughout the study period in septic shock patients than in trauma patients (p < .001). In septic shock patients, changes in both TNF-alpha and IL-6 were correlated with outcome, higher values being found in patients likely to die. Neither TNF-alpha nor IL-6 values were of any significant value in predicting outcome of trauma patients. When septic shock patients were compared with traumatized patients resuscitated from hemorrhagic shock, the former had much higher concentrations of both TNF-alpha and IL-6 throughout the study period (p < .01 to p < .00001). Increased IL-6 values were an indicator of the development of a nosocomial infection in trauma patients. In five trauma patients who developed a nosocomial pneumonia during the study period, the IL-6 concentration was 433 +/- 385 pg/mL before the onset of pneumonia, then peaked at 3970 +/- 1478 pg/mL on day 7, and returned to baseline (219 +/- 58 pg/mL) on day 11. CONCLUSIONS: In septic shock patients, high amounts of circulating TNF-alpha and IL-6 are found and then correlate with fatal outcome. In trauma patients (even those patients resuscitated from hemorrhagic shock), much less increased concentrations of IL-6 are detected while normal TNF-alpha circulating concentrations are measured. In these patients, cytokine concentrations do not correlate with outcome. This finding suggests a much higher degree of activation of the immunoinflammatory cascade in septic shock than in multiple trauma patients. Increased IL-6 values are an indicator of the development of a nosocomial infection in trauma patients.