Essential role for estrogen in protection against Vibrio vulnificus-induced endotoxic shock

Abstract

Little is known about the underlying mechanisms that result in a sexually dimorphic response to Vibrio vulnificus endotoxic shock. V. vulnificus is a gram-negative bacterium, considered one of the most invasive and rapidly fatal human pathogens known. However, 85% of individuals that develop endotoxic shock from V. vulnificus are males. Using the rat, we have developed a model for V. vulnificus endotoxic shock that mimics the sexually dimorphic response in humans. Gonadectomy in females results in increased mortality, and estrogen replacement results in decreased mortality in both gonadectomized males and females. These results demonstrate that estrogen is providing protection against V. vulnificus lipopolysaccharide-induced endotoxic shock.

FIG. 1

Mortality rate in female and male rats. Female (n = 19) and male (n = 11) rats were injected with intravenously with V. vulnificus LPS (30 to 50 μg/g of body weight). Mortality was determined as those animals that died within 24 h. A star indicates that statistically significant differences were found when chi-square analysis of the data was performed data followed by the sequential Bonferroni procedure (P < 0.05).

FIG. 2

Mortality rate in females with and without estrogen exposure. Female rats (n = 19), ovariectomized females (ovx females; n = 20), ovariectomized females injected with 1 μg of estradiol-17β per day for 5 days (ovx females E-1; n = 21), and ovariectomized females injected with 2 μg of estradiol-17β per day for 5 days (ovx females E-2; n = 16) were injected intravenously with V. vulnificus LPS (30 to 50 μg/g of body weight). Mortality was determined as those animals that died within 24 h. Stars indicate that statistically significant differences were found between mortality in the ovariectomized and ovariectomized females injected with 1 μg of estradiol-17β per day when compared to untreated females, but not between ovariectomized females injected with 2 μg of estradiol-17β per day and untreated females when chi-square analysis of the data was performed followed by the sequential Bonferroni procedure (P < 0.05).

FIG. 3

Mortality rate in mock-androgenized and androgenized females. Mock-androgenized (n = 16) and androgenized (n = 20) rats were injected intravenously with V. vulnificus LPS (30 to 50 μg/g of body weight). Mortality was determined as those animals that died within 24 h. An asterisk indicates that statistically significant differences were found when chi-square analysis of the data was performed followed by the sequential Bonferroni procedure (P < 0.05).

FIG. 4

Mortality rate in males with and without estrogen exposure. Female rats (n = 19), orchidectomized male rats (orch male; n = 11), orchidectomized males injected with 0.5 μg of estradiol-17β per day for 5 days (orch male E-0.5; n = 10), and orchidectomized males injected with 1 μg of estradiol-17β per day for 5 days (orch male E-1; n = 10) were injected intravenously with V. vulnificus LPS (30 to 50 μg/g of body weight). Mortality was determined as those animals that died within 24 h. Stars indicate that statistically significant differences were found between mortality in the orchidectomized males and that in orchidectomized males injected with 0.5 μg of estradiol-17β per day when compared to untreated females, but not between orchidectomized males injected with 1 μg of estradiol-17β per day and untreated females when chi-square analysis of the data was performed followed by the sequential Bonferroni procedure (P < 0.05).