Journal of Applied Physiology, Vol 64, Issue 5 2100-2107, Copyright © 1988 by American Physiological Society
Dexamethasone blocks increased leukotriene B4 production during endotoxin-induced lung injury
N. C. Olson, R. T. Dobrowsky and L. N. Fleisher
Department of Anatomy, Physiological Sciences and Radiology, College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
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.
