Response of psoriasis to a lymphocyte-selective toxin (DAB389IL-2) suggests a primary immune, but not keratinocyte, pathogenic basis.
Psoriasis is a hyperproliferative and inflammatory skin disorder of unknown aetiology. A fusion protein composed of human interleukin-2 and fragments of diphtheria toxin (DAB389IL-2), which selectively blocks the growth of activated lymphocytes but not keratinocytes, was administered systemically to ten patients to gauge the contribution of activated T cells to the disease. Four patients showed striking clinical improvement and four moderate improvement, after two cycle of low dose IL-2-toxin. The reversal of several molecular markers of epidermal dysfunction was associated with a marked reduction in intraepidermal CD3+ and CD8+ T cells, suggesting a primary immunological basis for this widespread disorder.
Gottlieb
S L
SL
Laboratory for Investigative Dermatology, Rockefeller University, New York, New York 10021-6399, USA.
Gilleaudeau
P
P
Johnson
R
R
Estes
L
L
Woodworth
T G
TG
Gottlieb
A B
AB
Krueger
J G
JG
D000328:Adult; D002454:Cell Differentiation; D002465:Cell Movement; D002478:Cells, Cultured; D004167:Diphtheria Toxin / Q000494:pharmacology*; D004817:Epidermis / Q000276:immunology; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D015603:Keratinocytes / Q000276:immunology; D008297:Male; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D004167:Diphtheria Toxin; D000922:Immunotoxins; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins; C078456:denileukin diftitox