INVESTIGATION ON A NOVEL AND SPECIFIC LEUKOTRIENE B-4 RECEPTOR ANTAGONIST IN THE TREATMENT OF STABLE PLAQUE PSORIASIS

The aim of the present study was to investigate the efficacy and clini cal tolerability of the specific leukotriene B-4 receptor antagonist V ML295 in the treatment of stable plaque psoriasis. Immunohistochemical and now cytometrical methods were used to assess the effects on infla mmation and epidermal proliferation, VML295 in the treatment of chroni c plaque psoriasis was shown to be safe and well tolerated. After trea tment, there was a statistically significant difference between patien ts treated with VML295 and patients treated with placebo with respect to the leukotriene B-4-induced CD11b up-regulation on the cell surface of polymorphonuclear leukocytes derived from peripheral blood. Ex viv o CD11b up-regulation in the VML295-treated group was completely inhib ited after 7 days of treatment (P = 0.001), This effect persisted unti l the end of the treatment period (P = 0.004 on day 15 and P <0.0001 a fter 4 weeks), whereas CD11b up-regulation in the placebo group remain ed unaffected. There was no statistically significant difference in th e median psoriasis area and severity index between the treatment group s at the end of the treatment period. During treatment, no significant histological changes were observed in the markers for cutaneous infla mmation and epidermal proliferation Although not statistically signifi cant, a tendency for the increased expression of some markers of cutan eous inflammation and epidermal proliferation was observed after 1 wee k. of treatment with VML295, and a decreased expression of these marke rs was seen after 4 weeks of treatment with VML295. This observation c ould indicate anti-inflammatory effects of VML295 appearing between 2 and 4 weeks after the start of treatment.