Suppressive effect of pentoxifylline on natural killer cell activity; experimental and clinical studies

Abstract

The methylxanthine derivative pentoxifylline, widely used in the treatment of vascular diseases, also has numerous immunological effects. In in vitro experiments, the human natural killer cell cytotoxicity was investigated in the presence of pentoxifylline. A clinical trial involved an investigation of the natural killer cell activity in patients to whom pentoxifylline had been administered for different periods. The natural cytotoxicity in macroangiopathic patients treated with pentoxifylline was compared with that in healthy controls and that in patients with vascular diseases who did not receive pentoxifylline therapy. A total of 62 macroangiopathic patients and 20 healthy controls were investigated. The natural killer cell activity in patients receiving pentoxifylline therapy for more than a year proved to be significantly lower (P<0.005). The presence of vascular disease did not influence the natural killer activity. In the in vitro cytotoxicity reaction, pentoxifylline at a concentration of 100 µg/ml was found to suppress the natural killer cell cytotoxicity at any stage of the reaction. The influence of pentoxifylline on the natural killer cell activity was not due to inhibition of the expression of intercellular adhesion molecule-1. However, this drug significantly decreases (P<0.05) the apoptosis of target cells. It is presumed that the suppressor effect of pentoxifylline on natural killer cell activity should be taken into consideration in the treatment of clinical diseases where this drug is administered chronically.