Investigation of Sexual Dimorphism in the Inflammatory Response to Biomaterials
K. Barry Delclos, Ph.D., National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079
The extent and resolution of the host inflammatory response induced by implantation of a foreign material plays a major role in determining the long-term success of an implanted medical device. Sexual dimorphism in the immune response is well documented in both animals and humans, and pilot projects were initiated to evaluate possible sex differences in the response to polydimethylsiloxanes (PDMS). Premenopausal women, postmenopausal women on hormone replacement therapy, and males age-matched to the females were recruited for the study. Premenopausal women were sampled in the luteal and follicular phases of the menstrual cycle, and the other groups were sampled twice at a similar interval. The chemiluminescent response to the materials was measured to determine the ability of the materials to activate cells in the absence of known cell stimulators. Subsequently, human serum-opsonized zymosan was added to measure the extent to which the phagocytic activity of the cells is modified by the materials. Whole blood and monocytes from females gave a significantly stronger oxidative burst to the materials than did cells from males. The inflammatory response in male and female Balb/c mice to subcutaneous PDMS implants was evaluated by histology and by immunohistochemical staining for the inflammatory mediators tumor necrosis factor-α and interleukin-1β (IL-1β). The reaction at the implant site was qualitatively similar in both males and females. The intensity of staining for the inflammatory mediators, particularly IL-1β, was stronger in the females at early time points. The response of females in these studies was modestly greater than that of males, but whether this difference is of sufficient magnitude to have long-term impact on the stability or performance of implanted devices remains to be determined.