LEUKOTRIENES IN THE SPUTUM AND URINE OF CYSTIC-FIBROSIS CHILDREN

1. Leukotrienes (LTs) are potent pro‐inflammatory mediators with actions relevant to the pathophysiology of cystic fibrosis (CF), including increased mucus production, bronchoconstriction, leucocyte chemotaxis, and increased vascular permeability. We have therefore investigated the potential role of LTs in children with CF. Leukotriene E4 levels were assessed in the urine of 30 normal (N) children (aged 1.3‐12.7 years) and 30 CF children (1.6‐14.3 years). Sputum from 13 of the CF children was analysed from LTB4, LTC4, LTD4, and LTE4. LTs were separated by reversed‐phase h.p.l.c. and quantitated by radioimmunoassay. 2. Urinary LTE4 levels were log normally distributed, with geometric mean values (95% confidence intervals) of N: 88.4 (71.3‐ 111) pmol mmol‐1 creatinine (n = 30), and CF: 112 (70.6‐177) pmol mmol‐ 1 creatinine (n = 30; P greater than 0.05). Of the CF subjects, 33% had urinary LTE4 levels above 200 pmol mmol‐1 creatinine, compared with 3.3% of the N children. 3. In sputum, mean (+/‐ s.e. mean) LT concentrations were (pmol g‐1), LTB4: 44.3 +/‐ 10.8, LTC4: 4.9 +/‐ 1.3, LTD4: 1.8 +/‐ 0.9, and LTE4: 67.7 +/‐ 18.9 (n = 13). 4. Urinary LTE4 levels correlated significantly with sputum LTE4 levels (r = 0.673, P = 0.012), and with sputum levels of total cysteinyl‐LTs (r = 0.660, P = 0.014). 5. In conclusion, total cysteinyl‐LT content in sputum is 10‐ fold higher than previously reported, consisting primarily (91%) of LTE4. The high levels of LTE4 and LTB4 in sputum suggest involvement of LTs in the pathophysiology of CF. Urinary LTE4 levels may prove useful as a marker for cysteinyl‐LT production in sputum. 1990 The British Pharmacological Society