Plasma and urinary leukotrienes in sickle cell disease: possible role in the inflammatory process

Abstract. Sickle cell (HbSS) disease is associated with rheological and inflammatory stresses within the microcirculation. In order to determine the role of leukotrienes in the inflammatory processes in HbSS patients, we analysed plasma and urine levels of leukotrienes (LT); LTB₄, LTC₄, LTD₄, and LTE₄ as indicators of their in vivo metabolism. Plasma and urine level samples of 15 HbSS patients in steady-state and age-matched healthy, homozygous (HbAA) controls were extracted for leukotrienes and quantitated by HPLC. Control plasma level of leukotrienes (mean ± SEM, ng ml^-1) were: LTB₄, 8·95 ± 0·26; LTC₄, 7·24 ± 0·21; LTD₄, 11·42 ± 0·40; and LTE₄, 14·51 ± 0·50. Corresponding values for HbSS patients were: LTB₄, 6·15 ± 0·42; LTC₄, 13·61 ± 1·45; LTD₄, 6·44 ± 0·51 and LTE₄, 4·97 ± 0·37. The differences were significant at P < 0·05. Urine levels (mean ± SEM, ng mmol^-1 creatinine), for controls were: LTB₄, 10·60 ± 0·35; LTC₄, 360·0 ± 9·82. Values for HbSS urine were: LTB₄, 27·50 ± 3·33; LTC₄, 356·0 ± 17·87; LTD₄, 69·90 ± 14·51. LTD₄ was not detected in control urine. These results suggest that sickle cell patients may exhibit impaired ability to catabolize LTC₄ in plasma during steady state conditions. This altered metabolism may contribute to the persistent stress of the microcirculation, and is probably related to the abnormal microvascular rheology of sickle blood cells.