Endogenous and exogenous glucocorticoids in experimental enterococcal infection.
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-alpha) response to both E. faecalis strains than did sham-adrenalectomized mice but that neither E. faecalis strain induced a systemic TNF-alpha response. Further, peritoneal TNF-alpha 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-alpha 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.
Papasian
Christopher J
CJ
Dept. of Basic Medical Science and Shock Trauma Research, M3-C03, UMKC School of Medicine, 2411 Holmes St., Kansas City, MO 64108, USA. papasianc@umkc.edu
Qureshi
Nilofer
N
Morrison
David C
DC
D000315:Adrenalectomy; D000818:Animals; D004198:Disease Susceptibility; D013293:Enterococcus faecalis; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000096:biosynthesis / Q000502:physiology*; D016908:Gram-Positive Bacterial Infections / Q000378:metabolism* / Q000401:mortality; D051379:Mice; D010537:Peritoneum / Q000378:metabolism / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha