INTERLEUKIN-8 IS INDUCED IN SKIN EQUIVALENTS AND IS HIGHEST IN THOSE DERIVED FROM PSORIATIC FIBROBLASTS

Interleukin-8 (IL-8) may be important in psoriasis as it is expressed in the stratum granulosum, attracts polymorphonuclear cells, and stimu lates angiogenesis and keratinocyte mitogenesis. To study intrinsic cu taneous factors in psoriasis, we constructed skin equivalents from pso riatic or adult control fibroblasts with normal foreskin keratinocytes . IL-8 levels were measured in supernatants by enzyme-linked immunosor bent assay and in skin equivalents by immunohistochemistry and in situ hybridization, IL-8 was highly induced in skin equivalents compared t o cells grown alone. Epidermal stratification varied among fibroblast lines and was correlated with IL-8 levels, but lesional and nonlesiona l psoriatic skin equivalents from the same donor were similar, Six fib roblast lines (two psoriasis lesion and four normal) supported only mo nolayers, while 12 lines (seven psoriasis lesion and five normal) prod uced stratification. Mean IL-8 levels were significantly lower in derm al equivalents of the first group than the second (0.78 +/- 0.40 vs 3. 93 +/- 2.83 ng per ml, mean +/- SD, p = 0.01, analysis of variance), S ignificantly more IL-8 was secreted by psoriatic than normal fibroblas t skin equivalents over 14 d (p = 0.015) with greatest differences at 1 and 4 d. Psoriatic IL-8 levels peaked first and remained increased. IL-8 protein and mRNA were initially strongest in dermal fibroblasts, and at the dermal-epidermal interface. Diffuse epidermal expression wa s replaced by accentuation in the stratum granulosum. Psoriatic skin e quivalents were thicker, had more intense IL-8 staining, and developed invagination. We hypothesize that an IL-8 paracrine loop between fibr oblasts and keratinocytes may play a key role in epidermal regeneratio n in the skin equivalent, in normal wound healing, and in the determin ation of an intrinsic psoriatic wound-healing phenotype.