PUVA BATH THERAPY STRONGLY SUPPRESSES IMMUNOLOGICAL AND EPIDERMAL ACTIVATION IN PSORIASIS - A POSSIBLE CELLULAR BASIS FOR REMITTIVE THERAPY

Psoriasis is characterized by alterations in both the epidermis and de rmis of the skin. Epidermal keratinocytes display marked proliferative activation and differentiate along an ''alternate'' or ''regenerative '' pathway, while the dermis becomes infiltrated with leukocytes, part icularly 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 correlate d the efficacy of PUVA bath therapy with its effects on specific molec ular and cellular parameters of disease, in 10 consecutive patients wi th recalcitrant psoriasis. Rapid clearing of lesions occurred in 8 out of 10 patients. Biopsies were taken from lesional and nonlesional ski n before and after a single round of therapy, and observation was cont inued in our Clinical Research Center at The Rockefeller University. E numeration of cycling keratinocytes with the Ki-67 monoclonal antibody showed that PUVA reduced eel proliferation by 73%. The pathological i ncrease in insulin-like growth factor 1 (IGF-1) receptors was reversed , whereas epidermal growth factor (EGF) receptors, which are also incr eased 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, loc alized to their normal sites. Epidermal and dermal T-lymphocytes (CD3( +)), as well as CD4(+), CD8(+), and IL-2 receptor(+) subsets, were str ongly suppressed by PUVA, with virtual elimination of IL-2 receptor(+) T cells in some patients. Consistent with diminished lymphocyte activ ation, HLA-DR expression by epidermal keratinocytes was markedly reduc ed in treated skin. In comparison to cyclosporine treatment of psorias is, PUVA therapy leads to more complete reversal of pathological epide rmal and lymphocytic activation, changes which we propose to be the ce llular basis for a more sustained remission of disease after PUVA trea tment.