Elevated concentrations of leukotriene D4 in pulmonary edema fluid of patients with the adult respiratory distress syndrome

Abstract

The possible contribution of metabolites of arachidonic acid to the increased permeability of the alveolar-capillary barrier in the adult respiratory distress syndrome was examined by quantifying the pulmonary edema fluid concentrations of lipoxygenase and cyclooxygenase products. The concentration of leukotriene D4 in pulmonary edema fluid of 10 patients with the adult respiratory distress syndrome (18.5 +/- 6.8 pmol/ml; mean +/- SD), assessed by specific radioimmunoassay after isolation of the mediator, was significantly higher (P less than 0.001) than that of five patients with cardiogenic pulmonary edema (4.4 +/- 1.1 pmol/ml). The concentrations of leukotrienes B4 and C4, prostaglandin E2, and thromboxane B2 in edema fluid were not significantly different in the adult respiratory distress syndrome patients than in the other subjects with pulmonary edema. The edema fluid concentration of leukotriene D4 correlated with the ratio of edema fluid to plasma concentrations of albumin (r = 0.64). Leukotriene D4 thus may contribute to the permeability defect which allows an accumulation of protein-rich alveolar fluid in the adult respiratory distress syndrome.

Prostaglandin E2 Mediates IL-1β-Related Fibroblast Mitogenic Effects in Acute Lung Injury through Differential Utilization of Prostanoid Receptors

“…However, our data using purified IL-1␤, and inhibitors of IL-1␤ signaling (i.e., IL-1ra and IL-␤-neutralizing Abs) clearly demonstrate that IL-1␤ is the predominant mediator of COX-2 induction and resultant PGE 2 production in adult human lung fibroblasts, in the context of ALI. The observations that PGE 2 levels were significantly higher (4-fold) in pulmonary edema fluid from patients with early ALI compared with HYDRO, and the positive correlation of edema fluid IL-1␤ Ag levels with that of PGE 2 Ag, further supports the in vivo relevance of our findings, and extends the increases in PGE 2 previously noted in a smaller group of patients (49).…”

Pathophysiology and pharmacological treatment of pulmonary hypertension in acute respiratory distress syndrome

“…LTB 4 is a potent neutrophil chemokine, whilst LTC 4 and LTD 4 cause pulmonary vasoconstriction, increased capillary permeability and pulmonary oedema formation. Clinical studies have demonstrated that increased levels of LTs have been found in the BALF taken from patients with ARDS [39]. It has also been shown that 5-lipoxygenase metabolites were elevated in BALF from sheep challenged with endotoxin [40,41].…”

The mercurial nature of neutrophils: still an enigma in ARDS?

“…It has been reported that the concentration of neutrophils in the bronchoalveolar lavage fluid (BALF) of patients with ARDS correlates with the severity of disease and with poor outcome (1,3,115). In addition to having elevated neutrophil numbers, BALF obtained from patients with ARDS is highly chemotactic for human neutrophils compared with BALF from normal subjects (141).…”