Comparative Effect of the Calcium Antagonist Verapamil and the Synthetic Steroids Gestrinone and Danazol on Human Monocyte Phagocytosis in vitro

Recent evidence suggested that periovulatory treatment with an immunomodulatory agent such as verapamil might be an effective alternative to conventional treatment for endometriosis-associated subfertility. In particular, it has been reported that the drug might reduce the accentuated macrophage peritoneal activation demonstrated in patients with endometriosis. In this study, we compared the effect of the calcium antagonist verapamil with those of gestrinone, danazol and testosterone on human monocyte phagocytosis in an attempt to evaluate any significant differences in their ability to influence a parameter of cell inflammatory activation. Peripheral blood monocytes were isolated from 37 healthy women. Monocyte function was determined by phagocytosis of fluorescent microspheres after an overnight incubation in the presence or absence of the various agents. This study indicates that verapamil at the pharmacological concentration of 0.4 micrograms/ml, the systemic level in patients taking 40-80 mg/8 h p.o., significantly inhibits monocyte function. A lower immunosuppressive but still significant effect was achieved in this assay system with gestrinone at a concentration of 3 x 10(-8) M). The pharmacological concentration of danazol (10(-6) M) and the physiologic concentration of testosterone (10(-8) M) did not significantly affect this immunologic test system. These results provide evidence that verapamil is able to exert a slightly greater immunosuppressive effect than steroidal drugs on monocyte phagocytosis. However, due to the small differences observed, further studies on the biological mechanism of the drug seem to be necessary to completely elucidate its potential role in endometriosis-associated subfertility.