leukotriene-e4 and Psoriasis

Cysteinyl leukotriene synthesis was investigated in patients with psoriasis. A non-invasive test requiring no stimulation was employed by measuring the major index metabolite of LTC4, which appears in urine. The presence of this metabolite, LTE4, was shown unequivocally by gas chromatography-mass spectrometry. Routinely LTE4 was quantitated by specific radio immunoassay after its isolation by reversed-phase high-performance liquid chromatography. Furthermore, in representative samples amounts of LTE4 obtained by radioimmunoassay were validated by gas chromatography-mass spectrometry. We demonstrate a significant (p less than 0.01) more than fourfold increase of urinary LTE4 in psoriasis compared to healthy volunteers. Urinary LTE4 was log normally distributed with geometric mean values (95% confidence intervals) of 11 (9-14) nmol LTE4/mol creatinine in healthy volunteers (n = 11) and 51 (28-95) nmol LTE4/mol creatinine in psoriasis (n = 9). The present study shows that cysteinyl leukotriene synthesis is enhanced in patients with psoriasis and that measurement of urinary LTE4 is a useful parameter to monitor its rate of synthesis.

Topics: Adult; Circadian Rhythm; Female; Gas Chromatography-Mass Spectrometry; Humans; Leukotriene E4; Male; Psoriasis; Radioimmunoassay; SRS-A

Gas chromatographic-(tandem) mass spectrometric (GC-MS(-MS)) methods for the analysis of cysteinyl leukotrienes (LTs) and leukotriene B4 (LTB4) in biological fluids were developed. The enzymatic synthesis of the stable-isotope labelled analogues [1,1-18O2] LTE4 and [14,15,17,17,18,18-2H6] LTB4 in high isotopic purity is described. Utilizing [1,1-18O2] LTE4 as an internal standard and GC-MS-MS enhanced cysteinyl LTs synthesis was found in patients with multiple trauma and psoriasis compared to healthy volunteers, respectively. The metabolism of LTB4 by human monocytes was investigated and two novel LTB4 metabolites were structurally identified by GC-MS as 10,11-dihydro-LTB4 and 10,11-dihydro-12-oxo-LTB4.

Topics: Gas Chromatography-Mass Spectrometry; Humans; Leukotriene B4; Leukotriene E4; Monocytes; Multiple Trauma; Psoriasis; SRS-A

The recent definition of the pathways of generation and structures of diverse products of the lipoxygenation of arachidonic acid has established the identity of a new family of mediators of hypersensitivity and inflammation. Studies of the effects of these mediators have shown that leukotrienes C, D, and E, the constitutents of the slow-reacting substance of anaphylaxis (SRS-A), are extremely potent smooth muscle contractile and vasoactive factors. Leukotriene B is a highly active stimulus of neutrophil and eosinophil functions and suppresses the immunological capabilities of T lymphocytes. The development of specific and sensitive radioimmunoassays has permitted the detection of elevated concentrations of leukotrienes in tissues or exudates in several diseases, including asthma, diverse allergic states, adult respiratory distress syndrome, psoriasis, spondyloarthritis, and gout. The application of selective inhibitors and antagonists of leukotrienes will clarify their pathogenetic contributions in human diseases and may yield new therapeutic approaches.

Topics: Arachidonate Lipoxygenases; Arachidonic Acids; Arthritis; Asthma; Cystic Fibrosis; Humans; Hypersensitivity; Leukotriene A4; Leukotriene B4; Leukotriene E4; Lipoxygenase; Psoriasis; SRS-A; Tears