PUVA bath therapy strongly suppresses immunological and epidermal activation in psoriasis: a possible cellular basis for remittive therapy.
Open Access
- 1 July 1994
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 180 (1), 283-296
- https://doi.org/10.1084/jem.180.1.283
Abstract
Psoriasis is characterized by alterations in both the epidermis and dermis of the skin. Epidermal keratinocytes display marked proliferative activation and differentiate along an "alternate" or "regenerative" pathway, while the dermis becomes infiltrated with leukocytes, particularly interleukin 2 (IL-2) receptor-bearing "activated" T cells. Psoralens, administered by the oral route, have therapeutic effects in psoriasis when photochemically activated by ultraviolet A light (PUVA therapy). Recently psoralen bath therapy has been introduced to more effectively deliver this agent to the diseased skin. We have correlated the efficacy of PUVA bath therapy with its effects on specific molecular and cellular parameters of disease, in 10 consecutive patients with recalcitrant psoriasis. Rapid clearing of lesions occurred in 8 out of 10 patients. Biopsies were taken from lesional and nonlesional skin before and after a single round of therapy, and observation was continued in our Clinical Research Center at The Rockefeller University. Enumeration of cycling keratinocytes with the Ki-67 monoclonal antibody showed that PUVA reduced cell proliferation by 73%. The pathological increase in insulin-like growth factor 1 (IGF-1) receptors was reversed, whereas epidermal growth factor (EGF) receptors, which are also increased in psoriasis, remained unchanged. Keratinocyte proteins that are expressed in abnormal sites of the epidermis during psoriasis, i.e., keratin 16, filaggrin, and involucrin, were, after PUVA treatment, localized to their normal sites. Epidermal and dermal T-lymphocytes (CD3+), as well as CD4+, CD8+, and IL-2 receptor+ subsets, were strongly suppressed by PUVA, with virtual elimination of IL-2 receptor+ T cells in some patients. Consistent with diminished lymphocyte activation, HLA-DR expression by epidermal keratinocytes was markedly reduced in treated skin. In comparison to cyclosporine treatment of psoriasis, PUVA therapy leads to more complete reversal of pathological epidermal and lymphocytic activation, changes which we propose to be the cellular basis for a more sustained remission of disease after PUVA treatment.Keywords
This publication has 43 references indexed in Scilit:
- Bath-water delivery of 8-methoxypsoralen therapy for psoriasisClinical and Experimental Dermatology, 1991
- Epidermal Keratiocytes Express the Adhesion Molecule Intercellular Adhesion Molecule-1 in Inflammatory Dermatoses.Journal of Investigative Dermatology, 1989
- Intercellular adhesion molecule-1 (ICAM-1) expression correlated to inflammationBritish Journal of Dermatology, 1989
- Photobiology 1937-1987.Journal of Investigative Dermatology, 1989
- Antipsoriatic, erythematogenic, and Langerhans cell marker depleting effect of bath—psoralens plus ultraviolet A treatment: Comparison of 8-methoxypsoralen and trimethylpsoralen photos ensitizationJournal of the American Academy of Dermatology, 1988
- Psoralen photochemotherapyJournal of the American Academy of Dermatology, 1987
- Flow cytometric quantification of T6-positive cells in psoriatic epidermis after PUVA and methotrexate therapyBritish Journal of Dermatology, 1987
- PUVA therapy for psoriasis: Comparison of oral and bath-water delivery of 8-methoxypsoralenJournal of the American Academy of Dermatology, 1986
- Relation of Antipsoriatic and Langerhans Cell Depleting Effects of Systemic Psoralen Photochemotherapy: A Clinical, Enzyme Histochemical, and Electron Microscopic StudyJournal of Investigative Dermatology, 1984
- The Use of Monoclonal Antibody to Keratin in Human Epidermal Disease: Alterations in Immunohistochemical Staining PatternJournal of Investigative Dermatology, 1983