ObjectiveTo study the frequency of several lymphocyte subsets, circulating cytokines, and prostaglandin plasma values at their time course over a period of 14 days in severely injured trauma patients in relation to the development of sepsis and multiple organ failure (MOF).DesignProspective study.SettingAn operative intensive care unit (ICU) of a university hospital.PatientsSixty-eight consecutive severely injured trauma patients.InterventionsPatients were separated into patients without sepsis and MOF (group 1, n = 51), and patients who developed sepsis and MOF (group 2, n = 17) during their stay in the ICU. Therapy was adjusted to the standards of modern intensive care management by physicians who were not involved in the study.Measurements and Main ResultsIn arterial blood samples, the profile of lymphocyte subset frequencies was performed by flow cytometry and, together with interleukin (IL)-1, IL-10, tumor necrosis factor (TNF)-alpha, soluble TNF-alpha receptor 1 (sTNF-alpha r1 [p55]), and prostaglandin E2(PGE2alpha)-alpha, serially measured after arrival in the ICU (baseline value) and during the next 14 days.Mean plasma IL-1 (29.3 +/- 5.8 [SD] pg/mL), TNF-alpha (138.5 +/- 22.4 pg/mL), and soluble TNF-alpha r1 (6.1 +/- 0.3 ng/mL) values were significantly higher in group 2 patients before clinical evidence of sepsis and MOF. With the onset of severe infections in group 2 patients, IL-1, TNF-alpha, and sTNF-alpha r1 values decreased, while immunosuppressive IL-10 (191.7 +/- 29.1 p g/mL) and PGE2alpha (87.7 +/- 20.4 pg/mL) values further increased and remained elevated during the time course. Analysis of lymphocyte subsets revealed a fall in total lymphocyte levels, in CD4+ T lymphocytes, and natural killer (NK) cells, but no change in CD8+ T lymphocyte subset. Despite a marked change in the T helper (CD4+) to T suppressor (CD8+) ratio (from 1:1.72 to 1:1.10), patients without MOF (group 1) had no significant difference in any of the markers tested compared with baseline values. In addition to the inverse CD4+/C D8+ T cell ratio (from 1:1.75 to 1:0.91) and increased activated T cells, each of these markers was significantly elevated and peaked before the onset of MOF in group 2 patients.ConclusionsA severely depressed cellular immune response associated with increased suppressive mediators might be closely related to the development of severe sepsis and MOF in trauma patients. Therefore, an in-depth understanding of the deficits in host defense following multiple trauma-will provide the basis for therapeutic interventions. (Crit Care Med 1999; 27:733-740)