Elevated levels of leukotriene B₄ and leukotriene E₄ in bronchoalveolar lavage fluid from patients with scleroderma lung disease

Abstract

Objective. The leukotrienes are a family of arachidonic acid-derived lipid mediators with proinflammatory and profibrotic properties. The aim of this study was to analyze the role of leukotriene B 4 (LTB 4 ) and LTE 4 in the pathogenesis of scleroderma lung disease (SLD).Methods. Nineteen systemic sclerosis (SSc) patients with SLD, 11 SSc patients without SLD, and 10 healthy controls were studied. Bronchoalveolar lavage (BAL) fluid was obtained during routine bronchoscopy of the right middle lobe in all study subjects. Levels of LTB 4 and LTE 4 were measured using enzyme immunoassay kits.Results. Levels of LTB 4 and LTE 4 were significantly higher in SSc patients with SLD (251 ؎ 170 pg/ml and 479 ؎ 301 pg/ml, respectively), than those in patients without SLD (114 ؎ 86 and 159 ؎ 149 pg/ml) and those in normal controls (86 ؎ 49 and 110 ؎ 67 pg/ml). In the total group of patients with SSc, levels of both leukotrienes correlated positively with the total number of cells in the BAL fluid and correlated negatively with the forced vital capacity. After intravenous pulse therapy with cyclophosphamide in 6 patients, there was a significant reduction in the concentration of LTB 4 (from 380 ؎ 196 pg/ml to 155 ؎ 123 pg/ml) but no significant difference in the levels of LTE 4 (from 697 ؎ 325 pg/ml to 418 ؎ 140 pg/ml).Conclusion. Our findings show that LTB 4 and LTE 4 levels are elevated in SSc patients with SLD and correlate with parameters of inflammation in the lungs. These results indicate that leukotrienes may contribute to the pathogenesis of SLD and may represent a new therapeutic target.

The role of leukotrienes in the pathogenesis of systemic sclerosis

“…Indeed, in the study by Tufvesson several patients received non-steroidal antiinflammatory drugs or steroids. These observations are of particular interest in view of our previous results showing that immunosuppressive treatment of SSc-ILD resulted in a significant decrease in the concentration of LTB4, but had no effect on LTE4, in the lungs of patients with SSc-ILD [20].…”

“…19]. High concentrations of LTB4 and LTE4 were found in the lungs of patients with SSc-ILD compared to SSc patients without SSc-ILD and healthy controls [20,21]. Concentrations of LTB4 and LTE4 had a significantly positive correlation with each other and with the fraction of inflammatory cells in bronchoalveolar lavage fluid (BALF).…”

“…Concentrations of LTB4 and LTE4 had a significantly positive correlation with each other and with the fraction of inflammatory cells in bronchoalveolar lavage fluid (BALF). The concentration of leukotriene LTB4 correlated positively with the percentage of neutrophils, which is considered a marker of local inflammation in the lower respiratory tract and a poor prognostic factor [20,22]. Moreover, concentrations of both LTB4 and LTE4 in the BALF negatively correlated with FVC [20].…”

“…The concentration of leukotriene LTB4 correlated positively with the percentage of neutrophils, which is considered a marker of local inflammation in the lower respiratory tract and a poor prognostic factor [20,22]. Moreover, concentrations of both LTB4 and LTE4 in the BALF negatively correlated with FVC [20]. These findings are in agreement with the study of Wilborn et al who showed that tissue homogenates obtained from patients with idiopathic pulmonary fibrosis (IPF), a prototypic fibrotic lung disease, contained 15-fold higher concentrations of LTB4, and five-fold higher levels of LTC4, compared to control samples of nonfibrotic lung tissue [23].…”

Modulation of Pulmonary Leukotriene B4 Production by Cyclooxygenase-2 Inhibitors and Lipopolysaccharide

“…In vitro smoking exposure significantly increased LTB4 production in ex-smokers' AMs with or without LPS stimulation, in the presence or absence of COX-2 inhibition (B; mean Ϯ SD; *, P Ͻ 0.05; n ϭ 3). monary disease, scleroderma lung disease, and malignancies, including that of lung cancer (1,14,(27)(28)(29)(30). To determine the effect(s) of COX-2 inhibitors on the 5-LOX signaling pathway in the lung microenvironment of active and former smokers, we evaluated the modulated release of LTB 4 under in vivo, ex vivo, and in vitro conditions.…”