Defective cytokine production early after multiple traumas: Modulation in severe sepsis

Abstract

Item does not contain fulltextThe exact time frame of multiple trauma-induced immunosuppression and the immune mechanisms mediating transition to severe sepsis are largely unknown. Peripheral blood mononuclear cells were isolated from 69 patients with multiple injuries within the first 24h from injury and from 36 healthy volunteers and stimulated for cytokine production. Circulating endotoxins were measured by the kinetic LAL assay. Measurements were repeated the first 24h of sepsis onset. Patients had defective responses for tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-10, IL-17 and interferon-gamma (IFNgamma) using a broad-panel of bacterial stimuli. Production of IFNgamma was pronounced for patients with trauma-related multiple organ failure (MOF). Thirty-six patients developed severe sepsis. At that time, production of TNFalpha was increased compared to baseline. The increase was greater among non-survivors than among survivors. Enhanced TNFalpha production on sepsis onset was a main finding of patients without endotoxemia. Immunosuppression of both innate and adaptive cytokine responses appears as early as the first 24h from injury. Transition into severe sepsis due to bacterial superinfection is accompanied by enhanced production of TNFalpha and this is linked with unfavorable outcome