Secretory leukocyte protease inhibitor, an inhibitor of neutrophil activation, is elevated in serum in human sepsis and experimental endotoxemia

Objectives: To document changes in serum secretory leukocyte protease inhib itor (SLPI) in human sepsis and in experimental endotoxemia in vivo. To com pare changes in serum SLPI in human sepsis with changes in interleukin (IL) -6, IL-10, and tumor necrosis factor (TNF)-alpha. To determine whether or n ot changes in SLPI correlate with the severity of multiple organ dysfunctio n syndrome as measured by the maximal multiple organ dysfunction score. Fin ally, because neutrophils have been implicated in tissue injury associated with organ dysfunction, to determine whether recombinant human SLPI blocks activation of isolated human neutrophils. Design. Case-control study and ex-vivo cellular assay. Setting: Surgical intensive care unit and clinical research center of unive rsity hospitals; laboratory of a medical school. Interventions: None. Measurements and Main Results: There was a significant dose-dependent eleva tion (50.2 +/- 4.0 ng/mL, p = .01) in plasma SLPI 12 hrs after administrati on of lipopolysaccharide to seven healthy adults (36.4 +/- 2.3 ng/mL). Furt her, serum concentrations of SLPI (132 +/- 15 ng/mL) were elevated in septi c surgical patients compared with healthy controls (43 +/- 2 ng/mL, p < .01 ) and nonseptic surgical controls (69 +/- 10 ng/mL, p = .01). Serum SLPI co ncentrations correlated (r(2) = .71, p < .01) better with organ dysfunction as measured by maximal multiple organ dysfunction score than did serum IL- 6 (r(2) = .49, p < .01), IL-10 (r(2) = .05, p = .22), or TNF-alpha (r(2) = .02, p = .44). We found that recombinant human SLPI in vitro inhibits TNF-a lpha-induced hydrogen peroxide production by human neutrophils (ID50 = 1-2 mu g/mL). Conclusions: Serum SLPI is elevated in human sepsis and experimental endoto xemia. Maximal concentrations of serum SLPI correlate significantly with ma ximal multiple organ dysfunction scores in patients with sepsis. Secretory leukocyte protease inhibitor may function to limit ongoing neutrophil-media ted tissue injury associated with organ dysfunction.