PLASMA AND URINARY LEUKOTRIENES IN SICKLE-CELL DISEASE - POSSIBLE ROLE IN THE INFLAMMATORY PROCESS

Sickle cell (HbSS) disease is associated with theological and inflamma tory stresses within the microcirculation. In order to determine the r ole of leukotrienes in the inflammatory processes in HbSS patients, we analysed plasma and urine levels of leukotrienes (LT); LTB(4), LTC(4) , LTD(4), and LTE(4) as indicators of their in vivo metabolism. Plasma and urine level samples of 15 HbSS patients in steady-state and age-m atched healthy, homozygous (HbAA) controls were extracted for leukotri enes and quantitated by HPLC. Control plasma level of leukotrienes (me an +/- SEM, ng ml(-1)) were: LTB(4), 8.95 +/- 0.26; LTC(4), 7.24 +/- 0 .21; LTD(4), 11.42 +/- 0.40; and LTE(4), 14.51 +/- 0.50. Corresponding values for HbSS patients were: LTB(4), 6.15 +/- 0.42; LTC(4), 13.61 /- 1.45; LTD(4), 6.44 +/- 0.51 and LTE(4), 4.97 +/- 0.37. The differen ces were significant at P < 0.05. Urine levels (mean +/- SEM, ng mmol( -1) creatinine), for controls were: LTB(4), 10.60 +/- 0.35; LTC(4), 36 0.0 +/- 9.82. Values for HbSS urine were: LTB(4), 27.50 +/- 3.33; LTC( 4), 356.0 +/- 17.87; LTD(4), 69.90 +/- 14.51. LTD(4) was not detected in control urine. These results suggest that sickle cell patients may exhibit impaired ability to catabolize LTC(4) in plasma during steady state conditions. This altered metabolism may contribute to the persis tent stress of the microcirculation, and is probably related to the ab normal microvascular theology of sickle blood cells.