BACTERICIDAL PERMEABILITY-INCREASING PROTEIN AMELIORATES ACUTE LUNG INJURY IN PORCINE ENDOTOXEMIA

Bactericidal/permeability-increasing protein (BPI), a cationic protein isolated from human neutrophils, binds lipopolysaccharide (LPS), kill s gram-negative bacteria, and neutralizes many of the effects of LPS i n vitro and in vivo. We hypothesized that a recombinant 23-kDa NH2-ter minal fragment of BPI (BPI23) would reduce acute lung injury in endoto xemic pigs. At -18 h, pigs received an intravenous priming dose of LPS (20 mu g/kg). Anesthetized ventilated swine were randomized to receiv e 1) no further treatment (n = 4); 2) LPS (250 mu g/kg over 50 min) an d BPI23 (3-mg/kg bolus and 3 mg/kg over 60 min) (n = 6); or 3) LPS and thaumatin, a cationic protein devoid of LPS neutralizing activity tha t has a molecular mass and isoelectric point that are similar to that of BPI23 (n = 7). BPI23 treatment significantly ameliorated LPS-induce d hypoxemia, functional upregulation of opsonin receptors on circulati ng phagocytes, and alveolitis but had no effect on the elaboration of tumor necrosis factor-alpha or thromboxane A(2). The salutory effects of BPI23 on acute lung injury in endotoxemic pigs may be mediated, at least in part, by inhibition of direct activation of phagocytes by LPS .