Pentoxifylline: a potent inhibitor of IL-2 and IFN-gamma biosynthesis and BCG-induced cytotoxicity

In the present study we investigated the influence of pentoxifylline (POF) on bacillus Calmette-Guérin (BCG)- and phytohaemagglutinin (PHA)-induced DNA synthesis and cytokine release, and BCG-induced cytotoxicity of human peripheral blood mononuclear cells (PBMC). DNA synthesis of PBMC stimulated with either BCG or PHA was inhibited by POF. We also demonstrated that the addition of POF led to a POF dose-dependent decrease of the release of the cytokines interleukin (IL)-2, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). The release of IL-6 remained unaffected. With respect to the inhibition of BCG-induced IL-2 and IFN-gamma release POF is active at the transcriptional (mRNA) level, as found by polymerase chain reaction (PCR). However, PHA-induced mRNA expression of these lymphokines is not affected by POF. Thus, the existence of a post-transcriptional regulation of PHA-induced cytokine release by POF can be assumed. The observed inhibition of cytokine release is correlated with a potent inhibitory effect of POF on BCG-induced cytotoxicity against bladder tumour cell lines. This effect is reversible.