ELEVATED TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) BIOLOGICAL-ACTIVITY IN PSORIATIC SKIN-LESIONS

Lesions of the common inflammatory skin disease psoriasis are characte rized by epidermal hyperproliferation, leucocyte adhesion molecule exp ression and leucocyte infiltration. The local release of proinflammato ry cytokines, such as TNF-alpha, may play an important role in the ind uction of these events. We have, therefore, analysed aqueous extracts of lesional and uninvolved (clinically normal) stratum corneum for the presence of TNF-alpha immunoreactivity and biological activity. TNF-a lpha immunoreactivity and bioactivity were consistently higher in lesi onal compared with uninvolved samples. By using an anti-TNF-alpha neut ralizing antibody it was demonstrated that the biological activity mea sured was due to the presence of TNF-alpha alone. Concentrations of so luble TNF receptors (p55 and p75) were also higher in lesional stratum corneum extracts, with the p55 form predominating. The plasma of psor iatic patients was also found to contain elevated concentrations of so luble p55 compared with normal controls. These results confirm the pre sence of immunoreactive TNF-alpha and, for the first time, conclusivel y demonstrate TNF-alpha biological activity and quantifiable concentra tions of soluble TNF receptors (p55 and p75) in lesional psoriatic sam ples. TNF-alpha recovery from stratum corneum probably reflects synthe sis in deeper, viable layers, where it is likely to exert its biologic al effects. Local and systemic release of soluble TNF receptors, in pa rticular p55, may serve to regulate the effects of TNF-alpha in psoria sis.