A vast amount of data has reported a distinct advantage in dermal wound healing in women compared to men. Our laboratory has repeatedly found an advantage in oral mucosal healing rates that favors men, implying that sex differences in healing rates are tissue dependent. Currently, the underlying mechanisms are unclear. Because mucosal tissue appears to heal optimally under conditions of reduced inflammation, this study objectively examined tissue inflammatory response after wounding in these same individuals, to help explain why women exhibit a disparity in oral mucosal healing rates.
Method:
470 healthy young adults (age range 18-35 years; 230 women) volunteered for this study. Two small excisional wounds were placed on the hard palate under local anesthesia, and were standardized for size, location, depth, and time of placement. Healing rates were determined using daily videographs. To assess inflammation, gene expression for interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α was determined directly in one of the wounds, biopsied at either 6h or 24h post-wounding, using real-time PCR.
Result:
Unwounded tissue (obtained at the time of wounding) did not exhibit differences in gene expression between sexes. However, women displayed a significantly higher inflammatory response than men 6h post-wounding, evidenced by increased gene expression for IL-6 and TNF-α. In addition, gene expression for IL-1β was elevated in women compared to men at 24h, suggesting that following injury women undergo prolonged inflammation of the mucosa.
Conclusion:
High inflammation in oral mucosa has been associated with slower healing in past studies. Here, women exhibited both higher and prolonged inflammation in oral wounds, suggesting a putative mechanism for explaining why women heal oral mucosal tissues more slowly than men. A better understanding of these underlying mechanisms would aid in the identification of therapeutic targets to potentially speed mucosal tissue repair in women.