DIFFERENTIAL MODULATION OF IL-8 AND TNF-ALPHA EXPRESSION IN HUMAN KERATINOCYTES BY BUFLOMEDIL CHLORHYDRATE AND PENTOXIFYLLINE

Pentoxifylline (PTX) is a methylxanthine derivative used in a wide ran ge of dermatoses. As well as its hemorrheologic activity, PTX has anti -inflammatory properties. Buflomedil chlorhydrate (BC) is another hemo rrheological drug with peripheral vasodilatory action, whose clinical uses are similar to those of PTX. Both drugs increase intracellular le vels of cAMP, either secondary to phosphodiesterase inhibition (PTX) o r adenyl-cyclase stimulation (BC). Long-term cultures of normal human keratinocytes were prepared in a free-serum medium, and stimulated wit h 1 mg/ml of phorbol 12-myristate 13-acetate (TPA) and PTX or BC (100- 1000 mu g/ml). Levels of TNF-alpha, IL-1 alpha, IL-1 beta, IL-8 and TG F-beta 1 using ELISA and Northern blot or RT-PCR techniques were measu red. TPA-induced TNF-alpha and IL-8 release from keratinocytes. TPA di d not induce IL-1 alpha or IL-1 beta release of keratinocytes. TPA inc reased RNA expression of the TNF-alpha, IL-1 alpha, IL-1 beta, IL-8 an d TGF-beta 1. BC diminished TPA-induced TNF-alpha and IL-8 release fro m keratinocytes; in the case of IL-8 it is possible that this inhibiti on occur to transcriptional level. Moreover PTX was unable to inhibit TNF-alpha and IL-8 synthesis and expression. PTX and BC reduced TPA-in duced IL-1 alpha and beta expression. It is possible that BC action is specifically exerted on keratinocytes, because we did not find simila r results with TNF-alpha and IL-8 synthesis in mononuclear peripheral blood cells.