Redondo P, García-Foncillas J, España A, Cuevillas F, Quintanilla E. Differential modulation of IL-8 and TNF-alpha expression in human keratinocytes by buflomedil chlorhydrate and pentoxifylline. Exp Dermatol. 1997 Aug;6(4):186-94.
Pentoxifylline (PTX) is a methylxanthine derivative used in a wide range of
dermatoses. As well as its hemorrheologic activity, PTX has anti-inflammatory
properties. Buflomedil chlorhydrate (BC) is another hemorrheological drug with
peripheral vasodilatory action, whose clinical uses are similar to those of PTX.
Both drugs increase intracellular levels of cAMP, either secondary to
phosphodiesterase inhibition (PTX) or adenyl-cyclase stimulation (BC). Long-term
cultures of normal human keratinocytes were prepared in a free-serum medium, and
stimulated with 1 mg/ml of phorbol 12-myristate 13-acetate (TPA) and PTX or BC
(100-1000 micrograms/ml). Levels of TNF-alpha, IL-1 alpha, IL-1 beta, IL-8 and
TGF-beta 1 using ELISA and Northern blot or RT-PCR techniques were measured.
TPA-induced TNF-alpha and IL-8 release from keratinocytes. TPA did not induce
IL-1 alpha or IL-1 beta release of keratinocytes. TPA increased RNA expression of
the TNF-alpha, IL-1 alpha, IL-1 beta, IL-8 and TGF-beta 1. BC diminished
TPA-induced TNF-alpha and IL-8 release from keratinocytes; in the case of IL-8 it
is possible that this inhibition occur to transcriptional level. Moreover PTX was
unable to inhibit TNF-alpha and IL-8 synthesis and expression. PTX and BC reduced
TPA-induced IL-1 alpha and beta expression. It is possible that BC action is
specifically exerted on keratinocytes, because we did not find similar results
with TNF-alpha and IL-8 synthesis in mononuclear peripheral blood cells.