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 action to cyclosporin A. We have investigated immunohistochemical changes in 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 reductions in dermal and epidermal CD4+ and CD8+ cells. Investigation of biopsies obtained 4-8 weeks after start of treatment revealed a significant fall in the numbers of activated mononuclear cells expressing CD25 (IL-2 receptor alpha-chain), HLA-DR, or CD11a (lymphocyte function-associated antigen-1, LFA-1 alpha chain). In contrast, the number of epidermal CD1+ (Langerhans) cells increased in response to FK 506 therapy. Study of leukocyte adhesion-related epitopes in active disease revealed 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 infiltrating mononuclear cells; ICAM-1 was also expressed weakly on epidermal keratinocytes. Vascular cell adhesion molecule-1 (VCAM-1) was either absent or expressed rarely on vascular endothelium. In response to FK 506 treatment, both ICAM-1 and E-selectin expression on blood vessels was reduced consistently but nevertheless persisted, even in individuals exhibiting total clearance of psoriatic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
Thomson
A W
AW
Pittsburgh Transplantation Institute, PA.
Nalesnik
M A
MA
Rilo
H R
HR
Woo
J
J
Carroll
P B
PB
Van Thiel
D H
DH
D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D019040:E-Selectin; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D016559:Tacrolimus / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D006684:HLA-DR Antigens; D016169:Lymphocyte Function-Associated Antigen-1; D015375:Receptors, Interleukin-2; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016559:Tacrolimus