Increased leukotriene B 4 in bronchoalveolar lavage fluid and plasma of endotoxemic pigs

Abstract

We hypothesized that leukotriene B 4 (LTB 4) might be produced during endotoxin-induced acute respiratory failure (ARF) observed in young pigs. We used radioimmunoassay (RIA) and reverse phase-high performance liquid chromatography (RP-HPLC) to determine the presence of LTB 4 in plasma and bronchoalveolar lavage fluid (BALF) of saline- and endotoxin-treated pigs. Endotoxin was infused at 5 μg/kg for 1 hour (hr) followed by 2 μg/kg/hr for an average of 3 hrs. Arterial plasma (collected at 0.5 hr intervals for 4 hrs) immunoreactive (i)-LTB 4 was significantly increased from 2.5 to 4 hrs of endotoxemia with the peak value occurring at 3.5 hrs (i.e. 282% of baseline value). Analysis of plasma extracts using RP-HPLC revealed an ultraviolet (UV) absorbance peak (270 nm) that was coincident with authentic LTB 4 standard. The levels of i-LTB 4 were significantly increased in BALF recovered from endotoxemic pigs (337 ± 71 vs 53 ± 13 pg/ml for saline controls). Endotoxin also increased the postmortem wet/dry ratio of bloodless lung and BALF albumin concentration, indicating pulmonary edema and increased permeability of the alveolar-capillary membrane, respectively. We conclude that LTB 4 is increased in plasma and BALF recovered from endotoxemic pigs and that this lipoxygenase metabolite could possibly be an important factor contributing to the pathophysiology of endotoxin-induced ARF.