REGULATION OF WHOLE-BLOOD TUMOR-NECROSIS-FACTOR PRODUCTION UPON ENDOTOXIN STIMULATION AFTER SEVERE BLUNT TRAUMA

Background: Trauma has been recognized to be accompanied by alteration s of leukocyte functions such as cytokine release, The regulatory prin ciples involved in these changes are still poorly defined, To further characterize leukocyte function after multiple trauma, endotoxin-stimu lated tumor necrosis factor (TNF) production of trauma patients' whole blood and a possible regulatory mechanism were studied. Methods: Endo toxin responsiveness in trauma patients (n 18, Injury Severity Score = 24 +/- 7) was assayed ex vivo using a whole blood model, TNF release and TNF alpha mRNA levels were determined during a 14-day period. Furt hermore, the influence of patients' sera on whole blood TSF production was evaluated. Main Results: The capacity of trauma patients' whole b lood to produce TNF was reduced for 1 to 6 days after trauma and was e qually evident for both TSF release and TNF alpha mRNA levels. The red uction of TNF coincides with the appearance of an inhibitor activity f or TNF production in trauma patients' sera, No correlation was found b etween the inhibitor, activity and soluble TSF receptors, endotoxin-ne utralizing molecules, inhibitor cytokines (interleukin 10 and transfor ming growth factor beta), or prostaglandins. Conclusions: Major trauma lends to the appearance of a circulating inhibitory activity for TNF synthesis that may potentially contribute to an anti-inflammatory resp onse in patients with multiple trauma. The elucidation of its structur al and functional properties may contribute to the understanding of th e pathogenesis of severely injured patients.