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


CONCLUSIONS
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.
Kowal-Bielecka
Otylia
O
Medical Academy of Bialystok, Bialystok, Poland.
Distler
Oliver
O
Kowal
Krzysztof
K
Siergiejko
Zenon
Z
Chwiećko
Justyna
J
Sulik
Agnieszka
A
Gay
Renate E
RE
Łukaszyk
Anna Bodzenta
AB
Gay
Steffen
S
Sierakowski
Stanisław
S
D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007275:Injections, Intravenous; D007975:Leukotriene B4 / Q000032:analysis / Q000378:metabolism*; D017999:Leukotriene E4 / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D020551:Pulse Therapy, Drug; D012595:Scleroderma, Systemic / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D007975:Leukotriene B4; D017999:Leukotriene E4; D003520:Cyclophosphamide