PMID: 15375608Sep 18, 2004Paper

Influence of pentoxifylline on perforin expression in human PBMC

International Journal of Molecular Medicine
Maciej LazarczykRobert Samaha

Abstract

Pentoxifylline (PTX) is a methylxanthine derivative that unspecifically inhibits phosphodiesterase activity and thus, it increases intracellular concentration of cyclic nucleotides. Currently, PTX is commonly and chronically used in peripheral blood vessel diseases. Besides its well-known influence on rheologic properties of blood, PTX has also been found to decrease secretion of some cytokines such as IL-12, TNF and IFN-gamma and thus it could exert immunomodulatory activity. Furthermore, PTX inhibits lymphocyte cytotoxicity affecting the perforin-dependent pathway, both in humans and animals. It has also been shown recently that in some murine models, PTX promotes tumor growth. Such a phenomenon, at least partially, could result from PTX-dependent inhibition of natural cytotoxicity. However, the detailed mechanism of PTX influence on cytotoxic activity in humans has not been established. We hypothesized that PTX-dependent inhibition of natural cytotoxicity could result from decrease in perforin expression. In this study, it was shown that pentoxifylline only moderately inhibits perforin expression at the mRNA level in human peripheral blood mononuclear cells (PBMC), and this effect seems to be independent of intracellular cAM...Continue Reading

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