ICAM-1 AND E-SELECTIN EXPRESSION IN LESIONAL BIOPSIES OF PSORIASIS PATIENTS RESPONDING TO SYSTEMIC FK-506 THERAPY

FK 506 is a new immunosuppressive agent with a similar molecular actio n to cyclosporin A. We have investigated immunohistochemical changes i n lesional biopsies of seven patients with severe recalcitrant chronic plaque psoriasis receiving systemic FK 506 therapy. Within 4 weeks of start of treatment, there was a striking reduction in psoriasis area and severity index (mean reduction 87.4%), accompanied by marked reduc tions in dermal and epidermal CD4+ and CD8+ cells. Investigation of bi opsies obtained 4-8 weeks after start of treatment revealed a signific ant fall in the numbers of activated mononuclear cells expressing CD25 (IL-2 receptor alpha-chain), HLA-DR, or CD11a (lymphocyte function-as sociated antigen-1, LFA-1alpha chain). In contrast, the number of epid ermal CD1+ (Langerhans) cells increased in response to FK 506 therapy. Study of leukocyte adhesion-related epitopes in active disease reveal ed strong expression of CD54 (intercellular adhesion molecule-1, ICAM- 1) and E-selectin (previously known as endothelial leukocyte adhesion molecule-1) both on microvascular endothelial cells and of ICAM-1 on i nfiltrating mononuclear cells; ICAM-1 was also expressed weakly on epi dermal keratinocytes. Vascular cell adhesion molecule-1 (VCAM-1) was e ither absent or expressed rarely on vascular endothelium. In response to FK 506 treatment, both ICAM-1 and E-selectin expression on blood ve ssels was reduced consistently but nevertheless persisted, even in ind ividuals exhibiting total clearance of psoriatic lesions. The results are consistent with interference by FK 506 with production of pro-infl ammatory cytokines, autocrine growth factors and the expression of adh esion molecules which are thought to regulate key interactions between keratinocytes, leukocytes and vascular endothelial cells in the patho genesis of psoriasis.