lactoferrin and Multiple-Organ-Failure

Forty patients with severe sepsis or septic shock recently received C1 inhibitor. In the present study we studied the effect of C1 inhibitor therapy on circulating elastase-alpha(1)-antitrypsin complex (EA) and lactoferrin (LF) levels in these patients to gain further insight about agonists involved in the activation of neutrophils in human sepsis. Elevated levels of EA and LF were found in 65 and 85% of the septic patients, respectively. Patients with elevated EA levels had higher organ dysfunction scores, higher levels of cytokines, and higher levels of complement activation products than patients with normal EA levels. C1 inhibitor therapy reduced EA as well as complement activation and IL-8 release in the patients with elevated EA on admission. We conclude that neutrophil activation in human sepsis correlates with the severity of organ dysfunction and involves complement and interleukin-8 as agonists. The effect of C1 inhibitor therapy on neutrophils may provide an explanation for the beneficial, although mild, effects of this treatment on organ dysfunction in sepsis.

Topics: Adult; Aged; alpha 1-Antitrypsin; Biomarkers; Complement Activation; Complement C1 Inactivator Proteins; Complement C1 Inhibitor Protein; Cytokines; Female; Humans; Interleukin-8; Lactoferrin; Leukocyte Elastase; Male; Middle Aged; Multiple Organ Failure; Neutrophils; Sepsis; Serpins; Shock, Septic

To investigate interactions between the endothelium and leukocytes in patients with sepsis, we measured soluble adhesion molecules (sE-selectin and sICAM-1), von Willebrand factor antigen (vWf:Ag), myeloperoxidase (MPO), and lactoferrin (Lacto-f) as plasma markers of endothelial and neutrophil activation. We tested whether the five proteins were predictors of clinical severity, which was evaluated by simplified acute physiological score (SAPS), number of organ failures (MOF), acute lung injury (ALI), and subsequent final outcome. Levels of the five plasma markers were higher in patients with severe infection (n = 25) than in patients without sepsis (n = 7) and healthy volunteers (n = 9). In the study population, levels of sE-selectin, sICAM-1, and vWf:Ag were higher for nonsurvivors as well as for patients with septic shock or with bacteremia, and they were correlated with SAPS and MOF. Survival outcome was predicted with high sensitivity and specificity by initial plasma levels of sICAM-1 and vWf:Ag. The initial sICAM-1 level appeared to be an independent prognostic variable, based on a logistic regression analysis. Unlike sE-selectin, sICAM-1 remained at high levels indefinitely in nonsurvivors. We conclude that, unlike neutrophil activation markers, levels of endothelium-derived soluble adhesion molecules and vWf:Ag in severe sepsis syndrome are correlated with the severity of illness and may be considered as predictors of survival outcome.

Topics: Adult; Aged; Aged, 80 and over; APACHE; Bacteremia; Biomarkers; E-Selectin; Endothelium, Vascular; Female; Follow-Up Studies; Forecasting; Humans; Intercellular Adhesion Molecule-1; Lactoferrin; Leukocytes; Logistic Models; Male; Middle Aged; Multiple Organ Failure; Neutrophil Activation; Peroxidase; Prognosis; Sensitivity and Specificity; Sepsis; Shock, Septic; Survival Rate; Treatment Outcome; von Willebrand Factor