Levels of antibodies to endotoxin and cytokine release in patients with severe trauma: does posttraumatic dysergy contribute to organ failure?

Abstract

We conducted a prospective study in patients with multiple injuries investigating the time course of trauma-related changes of systemic immunologic defense mechanisms. Patients with multiple injuries with Injury Severity Scores of more than 20 were included if they survived for more than 4 days after injury. Further inclusion criteria were no local or systemic infection (pneumonia, sepsis, soft-tissue infection, acquired immunodeficiency syndrome, tuberculosis, etc.) at the time of injury and no history of liver disease, bowel disease, or abdominal surgery. Serum endotoxin levels were measured from peripheral venous blood, as were the immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies against lipid A and against the core polysaccharide of endotoxin (lipopolysaccharide [LPS]), during the course of intensive care management. Serial central venous levels of interleukin-6 were determined as a marker of the inflammatory response. The patients were grouped according to their survival, with the survivors belonging to group S (48 patients) and the nonsurvivors belonging to group N (16 patients). The time of death for the nonsurvivors was between days 10 and 32 after the initial trauma. Thirteen of these patients (81%) died of multiple organ failure between days 12 and 17, two died of head trauma, and one died of sepsis. In patients who died of multiple organ failure, a significantly lower production of the IgM and IgG antibodies (AB) against lipid A and LPS was found before death (lipid A IgM-AB, day 11: group N, 29 +/- 11 U/mL; group S, 106 +/- 16 U/mL; p = 0.008; lipid A IgG-AB, day 11: group N, 18 +/- 9 U/mL; group S, 57 +/- 18 U/mL; p = 0.007; LPS IgM-AB, day 11: group N, 36 +/- 14 U/mL; group S, 122 +/- 23 U/mL; p = 0.009; LPS IgG-AB, day 11: group N, 17 +/- 12 U/mL; group S, 56 +/- 19 U/mL; p = 0.03). Interleukin-6 levels were significantly increased in the nonsurvivors (day 1: group N, 1,095 +/- 112 pg/mL; group S, 393 +/- 67 U/L; p = 0.008). In patients who died of severe trauma and in whom the cause of death was multiple organ failure, a significantly lower production of antiendotoxin antibodies was measured shortly before death. An insufficient immune defense (dysergy) may be involved in the pathomechanisms leading to the development of organ dysfunction.