Hormonal modulation of disseminating endodontic infections
OA Version
Citation
Abstract
OBJECTIVE: DEI sexual dimorphism has been observed where male but not female mice mildly immunosuppressed by blockade of IL-1 signaling, and challenged with an endodontic infection, developed facial abscesses, weight loss, splenomegaly, and sepsis which was often fatal. The central hypothesis is that estrogen increases the numbers and function of N1 neutrophils, resulting in effective anti- microbial immunity to DEI, whereas androgens are inhibitory. The aim of this study is to determine the effict of sex hormone modulation in protective immune responses to DEI and sepsis, specifically neutrophil-mediated resistance.
MATERIALS AND METHODS: The therapeutic effects of estrogen and the androgen receptor antagonist enzalutamide (ENZ) on DEI will be evaluated in adult male group through direct observation of facial abscess formation, fatigue, and malaise. Additionally, survival rates, weight change, and spleen weights will be recorded and compared between treatment groups. Male mice sub-groups will be categorized by hormonal treatments, which will be administered daily throughout a 31 day observation period after bilateral mandibular pulpal exposures and initiation of endodontic infections.
RESULTS: Group 1 received no estrogen and no enzalutamide treatment following pulpal exposures. And 7 mice (n=7) were included in the experiment, however 1 mouse’s final weight was unaccounted for due to the animal facility’s onsite veterinarian sacrificing and removing the mouse during their daily heath assessment. Throughout the course of the 31 day experimental timeline, average weight loss of this group was 4.72 grams. The average final spleen weight was 0.11 grams. Group 2 received enzalutamide treatment only following pulpal exposures and had a total of 12 mice (n=12). 2 mice were observed to have developed facial abscesses over the course of the 31 day hormone treatment period, and 8/12 survived to the end of the experimental period. Throughout the course of the 31 day experimental timeline, the average weight loss of this group was 3.63 grams. The average final spleen weight was 0.11 grams. Group 3 received estrogen treatment only following pulpal exposures and had a total of 8 mice (n=8). 2 mice did not survive the pulpal exposure procedure and accounted for the only mice that were lost in this group resulting in 6/8 mice surviving through the experimental period. Throughout the course of the 31 day experimental timeline, the average weight loss of this group was 3.66 grams. The average final spleen weight was 0.083 grams. Group 4 received both estrogen and enzalutamide treatment simultaneously, totaling in 11 mice (n=11). Throughout the experimental period, only 1 mouse was found deceased following the first round of hormonal treatments. Throughout the course of the 31 day experimental timeline, the average weight loss of this group was 1.45 grams. The average final spleen weight was 0.078 grams.
CONCLUSION: Estrogen’s (E2) has a protective role on immune cells and function against DEIs, while enzalutamide (ENZ) appears to effect protection minimally. Based on the comparisons between weight changes, spleen weights, and survival rates, a combination of E2 and ENZ resulted in the least overall weight loss and spleen weights throughout the course of the experiment while the groups that received no treatment and only ENZ resulted in the highest average weight loss and spleen weights.