INTERLEUKIN-1 RECEPTOR ANTAGONIST IN NORMAL AND PSORIATIC EPIDERMIS

The objective of these studies was to characterize the IL-1 inhibitory activity present in normal and psoriatic epidermis from clinically stable lesions. Fractionation of normal epidermal cytosol on a molecular sizing column failed to reveal the presence of IL-1 inhibitory bioactivity. However, specific ELISAs indicated that both the IL-1 receptor antagonist (IL-1ra) and IL-l-alpha were present in overlapping peaks. Further fractionation of the normal epidermal cytosol by anion exchange chromatography separated these two molecules, revealing the IL-1 inhibitory bioactivity of the IL-1ra molecule. Similar studies on psoriatic epidermal cytosol indicated the presence of IL-1 inhibitory bioactivity and IL-1ra protein. The IL-1 inhibitory bioactivity of both normal and psoriatic cytosol was neutralized by a mAb specific for IL-1ra. The ratio of IL-1ra to IL-1-alpha proteins was significantly increased in involved psoriatic skin compared with normal skin. By Western blot analysis this IL-Ira was almost-equal-to 20 kD, slightly larger than monocyte-derived IL-1ra and equivalent to an intracellular variant of IL-1ra expressed by keratinocytes. Polymerase chain reaction indicated the presence of mRNA for both forms of IL-1ra in normal epidermis, with both forms increased in psoriatic-involved skin. Immunofluorescence studies revealed the IL-1ra protein to be concentrated in the stratum granulosum of normal skin and in the basal-midbasal layers of psoriatic epidermis. These results suggest that the balance between intracellular IL-1ra and IL-l-alpha may be an important influence on keratinocyte growth and/or differentiation, as well as on the inflammatory potential of IL-1 in injured skin.