THE CYTOKINE NETWORK IN LESIONAL AND LESION-FREE PSORIATIC SKIN IS CHARACTERIZED BY A T-HELPER TYPE-1 CELL-MEDIATED RESPONSE

As a psoriatic lesion develops at sites of previously uninvolved skin, cytokines and their subsequent induction of various adhesion molecule s may play important pathophysiologic roles. To further define the cyt okine network in psoriasis, biopsies were obtained from both lesional skin and lesion-free skin of individuals with psoriasis and compared t o normal skin biopsies from control subjects. Each biopsy was analyzed using polymerase chain reaction for expression of cytokines and immun ostaining to detect adhesion molecules. The results indicate that psor iatic lesions have a type 1 cytokine profile (i.e., interleukin[IL]-2, interferon[IFN]-gamma, and tumor necrosis factor[TNF]-alpha), without a significant component of type 2 cytokines (i.e., IL-4, IL-5, and IL -10) accompanied by aberrant expression of endothelial cell leukocyte adhesion molecule (ELAM)-1 and vascular cell adhesion molecule (VCAM)- 1 on dermal endothelial cells, and ICAM-1 on epidermal keratinocytes. Four of five lesion-free biopsies from psoriatic patients had prominen t cytokine mRNA expression compared with skin from normal donors (part icularly TNF-alpha, IL-1alpha, IL-1beta, with lesser increases in IFN- gamma and granulocyte/macrophage colony-stimulating factor [GM-CSF]), which was accompanied by aberrant adhesion molecule expression in the same four samples. We conclude that a particular T-cell population pro ducing type 1 cytokines accumulates in psoriatic lesions. In addition, clinically lesion-free skin is characterized by increased levels of v arious cytokine mRNAs, and aberrant adhesion molecule expression in bo th dermal and epidermal compartments.