Urine leukotriene E4 levels are elevated in patients with active systemic lupus erythematosus

The peptidoleukotrienes, leukotriene (LT) C4 and its metabolites LTD4 and LTE4, cause diverse physiologic effects and have been implicated in several disease processes. A potential role for enhanced peptidoleukotriene synthesis in the pathogenesis of autoimmune disease in general and systemic lupus erythematosus (SLE) in particular has been suggested by animal studies. Therefore, we measured the urinary levels of LTE4 in patients with active and inactive SLE as well as in patients with rheumatoid arthritis (RA), scleroderma (Scl), and in healthy controls. Comparisons were made to other standard clinical tests in assessing individual patient disease activity. A marked increase in urinary LTE4 levels in patients with active SLE was noted (319 +/- 49 pg/mg creatinine, n = 20) relative to patients with inactive SLE (80 +/- 8 pg/mg creatinine, n = 7 [p less than 0.02]), patients with RA (86 +/- 8 pg/mg creatinine [p less than 0.01]), and healthy controls (68 +/- 4.3 pg/mg creatinine, n = 6 [p less than 0.01]). Patients with Scl also had elevated urinary LTE4 levels (188 +/- 33 pg/mg creatinine, n = 7) relative to controls (p less than 0.02), while values from patients with RA were not significantly different from controls. Using the Systemic Lupus Activity Measurement as a gauge of clinical activity, a rise in urinary LTE4 levels was noted during stages of active disease with a subsequent decline following the resolution of these symptoms. Our data indicate that increased synthesis of leukotrienes is associated with active SLE and Scl and suggest that these leukotrienes may mediate certain symptoms associated with these diseases.