leukotriene-b4 and Gram-Negative-Bacterial-Infections

Leukotriene B

Topics: 5-Lipoxygenase-Activating Proteins; Achromobacter denitrificans; alpha-Defensins; Animals; Bacterial Load; Cells, Cultured; Dinoprostone; Gram-Negative Bacterial Infections; Inflammation; Leukotriene B4; Lung; Macrophages, Alveolar; Mice; Mice, 129 Strain; Mice, Knockout; Phagocytosis; Receptors, Leukotriene B4; Signal Transduction

This study evaluated whether prostacyclin is a necessary mediator of inflammation in graded bacteremia or is sufficient alone in pathophysiologic concentrations to cause the pulmonary derangement of bacteremic shock.. Experimental.. Laboratory.. Twenty-three anesthetized adult swine. INTERVENSIONS: Swine were studied in four groups for 4 hrs: a) an anesthesia control group (n = 6); b) a septic control group (n = 6), in which 1010/mL Aeromonas hydrophila was infused intravenously at 0.2 mL.kg-1.hr-1 and increased to 4.0 mL.kg-1.hr-1 over 3 hrs; c) a prostacyclin infusion group (n = 6), which received prostacyclin infusion to match septic control plasma concentrationsclm without bacteremia; and d) an antiprostacyclin antibody group (n = 5), which received continuous Aeromonas hydrophila infusion plus antiprostacyclin antibody infusion.. Pulmonary hemodynamics, arterial blood gases, and plasma concentrations of arachidonate metabolites were measured hourly over a 4-hr period. In the septic control group and antiprostacyclin antibody group, elevated pulmonary vascular resistance index and pulmonary artery pressure with decreased Pao2, as well as lower pH, were documented after 1 and 3 hrs of graded bacteremia compared with the anesthesia control group and prostacyclin infusion group (p <.05). Thromboxane B2 concentration increased significantly in all groups during septic shock. In the antiprostacyclin antibody group, leukotriene B4 increased immediately after starting antiprostacyclin antibody infusion and reached significance at 3 hrs compared with the septic control group (p <.05). The prostacyclin infusion group had consistently lower concentrations of leukotrienes C4, D4, and E4 than all other groups.. Prostacyclin does not mediate blood gas changes, alterations of pulmonary hemodynamics, or platelet abnormalities in porcine septic shock, because antiprostacyclin antibody infusion did not change the pulmonary hypertension and hypoxemia, and infusion of prostacyclin to pathophysiologic blood concentrations did not reproduce such changes. Antiprostacyclin blockade during bacteremia significantly increased concentrations of leukotrienes C4, D4, and E4 and leukotriene B4, whereas prostacyclin infusion suppressed concentrations of leukotrienes C4, D4, and E4, suggesting that endogenous prostacyclin may blunt leukotriene release.

Topics: 6-Ketoprostaglandin F1 alpha; Analysis of Variance; Animals; Antihypertensive Agents; Bacteremia; Epoprostenol; Gram-Negative Bacterial Infections; Hemodynamics; Hypertension, Pulmonary; Leukotriene B4; Lung Diseases; Matched-Pair Analysis; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Shock, Septic; SRS-A; Swine; Thromboxane B2

The hypothesis was tested that polymorphonuclear leukocytes (PMNL) from patients with gram-negative bacteremia are primed to produce leukotriene B4 (LTB4) or 5-hydroxyeicosatetraenoic acid (5-HETE), in response to concentrations of calcium ionophore A23187, which are substimulatory for control PMNL. PMNL from 11 bacteremic patients and 8 healthy subjects (11 samples) produced similar quantities of LTB4, omega-oxidation products of LTB4, and 5-HETE after incubation with 0.3 and 0.5 microM A23187 for 5 min. At the detection threshold of 0.3 microM A23187, LTB4 was present in PMNL preparations from 9 of 11 patients and 7 of 11 control samples and 5-HETE from the same 9 patients and from 6 controls. There was no correlation between LTB4 or 5-HETE and plasma levels of endotoxin. In this group of patients, priming of PMNL by gram-negative bacteremia did not lead to enhanced production of LTB4, its omega-oxidation products, or 5-HETE when PMNL were challenged with low concentrations of A23187.

Topics: Adult; Aged; Aged, 80 and over; Bacteremia; Calcimycin; Endotoxins; Female; Gram-Negative Bacterial Infections; Humans; Hydroxyeicosatetraenoic Acids; Leukotriene B4; Male; Middle Aged; Neutrophils