Increased leukotriene B4 in bronchoalveolar lavage fluid and plasma of endotoxemic pigs.

We hypothesized that leukotriene B4 (LTB4) 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 LTB4 in plasma and bronchoalveolar lavage fluid (BALF) of saline- and endotoxin-treated pigs. Endotoxin was infused at 5 micrograms/kg for 1 hour (hr) followed by 2 micrograms/kg/hr for an average of 3 hrs. Arterial plasma (collected at 0.5 hr intervals for 4 hrs) immunoreactive (i)-LTB4 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 LTB4 standard. The levels of i-LTB4 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 LTB4 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.