Epidermal expression of interleukin-6 and tumour necrosis factor-alpha in normal and immunoinflammatory skin states in humans

Abstract

The in vivo presence of cytokines in human skin was examined by ABC- and IF-techniques, and by using antisera to human rIL-6, rIL-1-alpha, rIL-1-beta, rTNF-alpha and an antiserum to crude supernatants of Staph. albus activated human blood monocytes (anti-MK-antiserum) before and after absorption with rIL-6. The following normal and immunoinflammatory human skin states were examined: Normal skin. Examination of biopsies from 9 healthy individuals and single cell preparations from 3 healthy individuals revealed a granular intercellular/membrane associated staining for IL-6 and TNF-alpha in the upper epidermal layers. A cytoplasmic staining was also detected, most pronounced using the anti-rIL-6 antiserum. Membrane associated IL-6 and TNF-alpha were detected in epidermal single cell preparations, but CD1 positive LC failed to express any of the cytokines examined. Psoriasis skin. Biopsies from lesional and unaffected skin of 11 patients with chronic, nummular/plaque type psoriasis were investigated for IL-6, and in addition 5 of these, moreover, for TNF-alpha. Biopsies from lesional psoriatic skin continually revealed increased staining for IL-6 compared with non-lesional skin, where the staining was similar to that observed in healthy individuals. Epidermal TNF-alpha expression did not differ from that observed in normal skin. AIDS related Kaposi's sarcom. Epidermal staining patterns were similarly increased for IL-6 and TNF-alpha in biopsies obtained from nodular KS tumours compared with unaffected skin of 6 homosexual male AIDS patients, whereas the endotheloid cell of the tumour did not stain for any of the cytokines. Staining of unaffected skin was similar to that observed in healthy individuals. The allergic and irritant patch test reaction. Investigation of biopsies from 5 patients with positive APR and 5 healthy individuals with IPR disclosed increased epidermal staining for IL-6, but not for TNF-alpha, in both reactions, while staining from petrolatum tested and non-tested skin was similar to that observed in normal individuals. CD1 positive LC remained negative in all biopsies when stained for IL-6 and TNF-alpha. In vivo UV-irradiated skin. Using anti-MK and anti TNF-alpha antisera skin biopsies from 5 healthy subjects 24 h after UVB irradiation revealed markedly increased epidermal staining for both cytokines compared with non-irradiated skin. Furthermore, a gradual decrease in epidermal staining for IL-6 was observed in specimens from lesional skin of 6 patients with psoriasis taken before and during PUVA therapy, while staining of non-lesional skin remained unchanged.