Endogenous and Exogenous Glucocorticoids in Experimental Enterococcal Infection

Abstract

The potentially protective role of the host adrenal-glucocorticoid response to enterococcal infection was evaluated in an experimental model in which mice were infected intraperitoneally with two distinct Enterococcus faecalis strains (K9 and CP-1). We demonstrated that corticosterone levels in serum and peritoneal-lavage fluid were elevated within 1 hour of infection with either E. faecalis strain. We also demonstrated that adrenalectomized mice generated a more robust localized peritoneal tumor necrosis factor alpha (TNF-␣) response to both E. faecalis strains than did sham-adrenalectomized mice but that neither E. faecalis strain induced a systemic TNF-␣ response. Further, peritoneal TNF-␣ production in adrenalectomized mice infected with either E. faecalis K9 or CP-1 was suppressed by prior treatment with an exogenous glucocorticoid (dexamethasone). The potential clinical significance of these results was suggested by our findings that adrenalectomy markedly increased susceptibility (a >100-fold decrease in the 50% lethal dose) to lethal infections with E. faecalis CP-1 and that prior dexamethasone treatment partially compensated for adrenalectomy. In marked contrast to these findings, however, adrenalectomy did not substantially increase susceptibility to lethal E. faecalis K9 infection. Further, preinfection with E. faecalis CP-1 1 hour before infection with E. faecalis K9 did not protect mice from lethal E. faecalis K9 infections. Collectively, these studies indicate that the host can generate a glucocorticoid response to E. faecalis infection that suppresses TNF-␣ production. Further, this glucocorticoid response can protect the host from potentially lethal E. faecalis infections, but different strains show heterogeneity with respect to the extent of protection afforded by the adrenal-glucocorticoid response.

Adrenal hormone deprivation affects macrophage catecholamine metabolism and β2‐adrenoceptor density, but not propranolol stimulation of tumour necrosis factor‐α production

“…Adrenalectomy increased the LPS‐stimulated TNF‐α production by peritoneal macrophages, and this effect was completely abrogated by corticosterone supplementation. This was consistent with data indicating that the expression of pro‐inflammatory cytokines, including TNF‐α, is repressed by glucocorticoids (Tuckermann et al 2005) and that adrenalectomized mice generate a more robust localized peritoneal TNF‐α response to Enterococcus faecalis infection, which can be completely suppressed by prior treatment with dexamethasone (Papasian et al 2006). It should be noted that adrenal glucocorticoid withdrawal may indirectly influence, at least partly, TNF‐α production through the stimulation of macrophage corticotrophin‐releasing hormone synthesis and release (Robinson et al 1988; Karalis et al 1991; Agelaki et al 2002).…”

Butterflies in the gut: the interplay between intestinal microbiota and stress

“…E. faecalis AG5 can increase both long- and short-chain fatty acids in the host, which might indirectly affect the nervous system through an indirect fashion [ 228 ]. One report found that infection of mice with pathogenic E. faecalis strains, K9 and CP-1 , increased corticosterone in an acute manner, suggesting that E. faecalis can alter glucocorticoid signaling in the host [ 229 ]. Clinically, E. faecalis was present in 89.3% of healthy controls, whereas only in 58.3% of neurodevelopmental disorders, 58.3% of mixed specific developmental disorders, and 55.6% of expressive and receptive language disorder [ 230 ].…”