Silicone-induced modulation of natural killer cell activity.

Current controversy regarding the effects of silicone gel mammary implants on the immune system has led to increased focus on the potential biological activity of silicone materials. Studies were undertaken in the B6C3F1 mouse to evaluate the immunotoxicological effects of the following components of a mammary gel prosthesis: polydimethylsiloxane fluid, silicone gel, elastomer shell and a polyurethane implant cover. Material was implanted subcutaneously (s.c.) for either 10 or 180 days. The only toxicological or immunological parameter which differed from control values was the natural killer (NK) cell activity in gel implanted mice. In these animals, basal NK activity was decreased. NK activity was comparably inhibited in female Fischer 344 rats implanted with silicone gel following short term (14 or 30 days) as well as chronic (1 year) exposure. The response was variable in both the rat and mouse. Host resistance to B16F10 melanoma in the mouse is known to be related to NK activity. Despite suppression of NK activity following gel implantation, host resistance was unaltered. Inhibition of NK activity by the administration of anti-asialo GM1 indicated that resistance was not adversely affected until NK activity was decreased by 40 to 50%. As with basal NK activity, augmented NK activity was inhibited in gel implanted rats when compared to controls. Administration of polyinosinic:polycytidylic acid to gel implanted rats resulted in an increase of approximately 65% in NK activity compared to gel implanted controls. This level of augmented NK activity was significantly less than the level of augmented NK activity in vehicle implanted animals where 100% enhancement in NK activity was noted. The results of these studies indicate that (1) NK cytolytic activity is altered in two animal models, the mouse and rat, although the results were variable, that (2) the level of suppression noted in the mouse is ineffective when compared to the level of suppression required to alter host resistance to B16F10 melanoma and that (3) the gel implanted animals exhibit a suppressed response to NK augmentation.