Dexamethasone blocks increased leukotriene B4 production during endotoxin-induced lung injury.
We hypothesized that leukotriene B4 (LTB4) might be produced during endotoxemia in pigs and, if so, might play a role in the pathophysiology of acute respiratory failure. Escherichia coli endotoxin (055-B5) was infused intravenously into anesthetized pigs at 5 micrograms/kg the 1st h, followed by 2 micrograms.kg-1.h-1 for 3 h. Endotoxemic pigs were treated with dexamethasone (DEX, iv) 18 h (5 mg/kg) and 1 h (5 mg/kg) before onset of endotoxemia. During phases I (i.e., 0-2 h) and II (i.e., 2-4 h), endotoxin decreased cardiac index, caused granulocytopenia, and increased mean pulmonary arterial pressure, pulmonary vascular resistance, alveolar-arterial O2 gradient, and hematocrit. During phase II, plasma LTB4 levels were increased (as determined by radioimmunoassay, reverse-phase high-performance liquid chromatography, and ultraviolet spectroscopy). Endotoxin increased the levels of LTB4 and albumin in bronchoalveolar lavage fluid (BALF). DEX blocked or greatly attenuated the endotoxin-induced hemodynamic abnormalities and blocked the increases in plasma and BALF LTB4 levels. We conclude that LTB4 is produced during porcine endotoxemia and could possibly play a role in the pathophysiology of endotoxin-induced lung injury in anesthetized pigs.
Olson
N C
NC
Department of Anatomy, Physiological Sciences and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
Dobrowsky
R T
RT
Fleisher
L N
LN
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D007975:Leukotriene B4 / Q000096:biosynthesis*; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000378:metabolism; D013552:Swine
D004731:Endotoxins; D007975:Leukotriene B4; D003907:Dexamethasone