Longitudinal studies of inter-alpha inhibitor proteins in severely septic patients: a potential clinical marker and mediator of severe sepsis.

Objective: To determine the clinical relevance and prognostic significance of serial measurement of inter-alpha inhibitor proteins (lalp) in severely septic patients. Design: A laboratory-based study of serial plasma samples over the first 5 days of severe sepsis from a prospective clinical trial. Setting: Small business and academic medical center research laboratories. Patients: Two hundred sixty-six patients with severe sepsis from a multiple-center phase III clinical trial. Interventions: None. Measurements and Main Results: Inter-alpha inhibitor proteins serve as endogenous serine protease inhibitors in human plasma. The levels of lalp were markedly reduced to a mean value of 290 ± 15 μg/mL at the onset of severe sepsis compared with normal plasma levels (617 ± 197 μg/mL). Failure of lalp levels to recover over the first 5 days of sepsis was associated with an unfavorable outcome (p <.001). IαIp levels were inversely correlated with interleukin-6 levels at study entry and over the first 5 days of management of severe sepsis. IαIp levels were significantly lower in women, with increased age, in the presence of multiple organ failure and in patients with intra-abdominal sources of sepsis. Conclusions: Inter-alpha inhibitor proteins are markedly reduced in severe sepsis, and failure of recovery of lalp levels over the course of sepsis is associated with an unfavorable outcome.