Uses for pentoxifylline or functional derivatives/metabolites thereof

摘要

In accordance with the present invention, it has been discovered that monocyte conditioned medium (MCM) obtained from patients with liver disease stimulates the proliferation of fibroblasts. Platelet derived growth factor (PDGF) has also been found to stimulate fibroproliferation of fibroblasts, and to be at least partially responsible for the fibroproliferative effect of the MCM. Further in accordance with the present invention, the effect of MCM and PDGF on the expression of c-fos and c-jun has been investigated, because c-fos and c- jun form AP-1 complexes which can stimulate genes involved in proliferation. It has recently been reported that pentoxifylline inhibits platelet derived growth factor-stimulated proliferation. The mechanism of this action of pentoxifylline is unclear. Thus, in the course of the work undertaken as part of the present invention, studies were conducted to determine whether pentoxifylline altered the expression of c-fos and c- jun. While PDGF was found to induce the expression of both c-fos and c- jun, pentoxifylline was found to effectively reduce the effect of PDGF- induced c-jun gene expression, without altering c-fos gene expression. These results suggest that pentoxifylline inhibits PDGF stimulated proliferation by decreasing c-jun expression. These results further suggest a variety of diseases and/or conditions which may also be successfully treated with pentoxifylline.