<b>Adrenalitis and the adrenocortical response of resistant and susceptible mice to acute murine cytomegalovirus infection</b>

Price, Patricia; Olver, Stuart D.; Silich, Marina; Nador, T. Z.; Yerkovich, Stephanie T.; Wilson, Scott G.

doi:10.1046/j.1365-2362.1996.2210562.x

Cited by 27 publications

(18 citation statements)

References 26 publications

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“…This may reflect genetic differences between both strains, since the animals were kept in the same animal facilities and were subjected to similar experimental conditions. In support of this possibility, Balb/c mice, compared to C57Bl/6J mice, have been reported to respond to certain types of stress (Lu et al 1998) and virus (Price et al 1996) with stronger stimulation of the HPA axis. We and others (Leite de Moraes et al 1991, Roggero et al 2002, Mantuano-Barradas et al 2003 have shown that during the acute phase of T. cruzi infection, there is a marked thymus atrophy, mainly characterized by the loss of CD4 C CD8 C cells.…”

Section: Discussionmentioning

confidence: 92%

Endogenous glucocorticoids cause thymus atrophy but are protective during acute Trypanosoma cruzi infection

Roggero¹,

Pérez²,

Kakazu³

et al. 2006

Journal of Endocrinology

116

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The cytokine-mediated stimulation of the hypothalamuspituitary-adrenal (HPA) axis is relevant for survival during bacterial endotoxemia and certain viral infections. However, only limited information is available regarding the effects of endogenous glucocorticoids on parasite diseases. We have studied this issue using, as a model, C57Bl/6 and Balb/c mice infected with Trypanosoma cruzi, the causal agent of Chagas' disease. These two mouse strains differ in the susceptibility to infection with the parasite. An intense stimulation of the HPA-axis was observed 3 weeks after infection in both strains, but glucocorticoid levels were already increased two-to threefold in the less susceptible Balb/c strain during the first week. Blockade of glucocorticoid receptors with the glucocorticoid antagonist RU486, starting on day 10 after infection, partially reversed the thymic atrophy and decreased the number of CD4 C CD8 C thymocytes without affecting parasitemia and the number of inflammatory foci in the heart. However, tumor necrosis factor-a blood levels were increased in infected mice of both strains treated with RU486. Furthermore, the blockade of glucocorticoid receptors accelerated death in C57Bl/6J mice and increased lethality to 100% in Balb/c mice. The results obtained represent the first evidence that an endocrine host response that is coupled to the immune process can strongly affect the course of a parasite infection.

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Section: Discussionmentioning

confidence: 92%

Endogenous glucocorticoids cause thymus atrophy but are protective during acute Trypanosoma cruzi infection

Roggero¹,

Pérez²,

Kakazu³

et al. 2006

Journal of Endocrinology

116

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“…This increased mortality following adrenalectomy was correlated with increases in levels of the cytokines IFN , TNF and IL-6 (Ruzek et al 1999). In another study, adrenalectomy of BALB/c, but not C57BL/6, mice increased the mortality rates from MCMV virus (Price et al 1996). In the study by Price et al 4 10 4 pfu (plaque-forming units) MCMV virus was used, and 85% of the adrenalectomized C57BL/6 mice survived (Price et al 1996).…”

Section: Viral Infectionsmentioning

confidence: 95%

“…The kinetics of glucocorticoid release is both virus-specific and specific to the phase of the response, and is also influenced by the route of exposure. The murine cytomegalovirus (MCMV) (Price et al 1996, Ruzek et al 1997, Pearce et al 2001, lymphocytic choriomeningitis virus (LCMV) , Pearce et al 2001 and poly (I:C) (a synthetic viral analog) induced increases in glucocorticoid levels (Ruzek et al 1997, Pearce et al 2001. Furthermore, MCMV virus and poly (I:C) have been shown to induce glucocorticoid release through an interleukin (IL)-6-dependent pathway (Ruzek et al 1997).…”

Section: Viral Hpa Axis Activationmentioning

confidence: 99%

“…Increased mortality Reduced mortality Gonzalo et al 1993 MCMV virus Increased mortality Reduced mortality Price et al 1996, Ruzek et al 1999 50 µg LPS toxicity in adrenalectomized BALB/c mice, whereas 10 mg/kg corticosterone was ineffective (Butler et al 1989). In another study, 500 µg dexamethasone prevented 50 µg LPS toxicity in adrenalectomized CF1 mice, whereas a combination of 400 µg corticosterone and 200 µg deoxycorticosterone was ineffective.…”

Section: Staphylococcus Aureus Enterotoxin B (Seb)mentioning

confidence: 99%

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Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products

Webster

Sternberg

2004

Journal of Endocrinology

164

124

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The hypothalamic-pituitary-adrenal (HPA) axis is activated during many bacterial and viral infections, resulting in an increase in circulating glucocorticoid levels. This HPA axis activation and glucocorticoid response are critical for the survival of the host, as demonstrated by the fact that removal of the HPA axis (by adrenalectomy or hypophysectomy) or glucocorticoid receptor (GR) blockade enhances the severity of the infection and in some cases enhances the mortality rate. Replacement with a synthetic glucocorticoid reverses these effects by reducing the severity of the infection and provides protection against lethal effects. In addition, some bacteria and viral infections have been shown to affect the GR directly. These have been described and the implications of such an effect discussed.

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“…[4][5][6][7][8][9][10][11][12] Previous work by our group and others has demonstrated that removal of glucocorticoids (via adrenalectomy (ADX)) during viral infection is associated with elevations in plasma and tissue concentrations of proinflammatory cytokines and renders animals more susceptible to septic shock and death. [13][14][15] In addition, in the case of infection with murine cytomegalovirus (MCMV), a cytopathic virus that induces an early natural killer cell-mediated, anti-viral defense accompanied by elevations in plasma TNF-alpha, IL-1 and IL-6, 15 the increased death rate in adrenalectomized, MCMV-infected, animals can be reversed by glucocorticoid replacement. 15 Previous studies also have shown that the MCMV-induced corticosterone response, which parallels peak plasma cytokine concentrations and occurs around 36 h after infection, is dependent on IL-6.…”

Section: Introductionmentioning

confidence: 99%

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

Silverman

MacDougall

et al. 2006

Mol Psychiatry

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Endogenous glucocorticoids restrain proinflammatory cytokine responses to immune challenges such as viral infection. In addition, proinflammatory cytokines induce behavioral alterations including changes in locomotor/exploratory activity. Accordingly, we examined proinflammatory cytokines and open-field behavior in virally infected mice rendered glucocorticoid deficient by adrenalectomy (ADX). Mice were infected with murine cytomegalovirus (MCMV), and open-field behavior (36 h post-infection) and plasma concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 (42 h post-infection) were assessed. Compared to sham-ADX-MCMV-infected animals, ADX-MCMV-infected mice exhibited significant reductions in total distance moved, number of center entries, and time spent in center. These behavioral alterations were accompanied by significantly higher plasma concentrations of TNF-alpha and IL-6, both of which were correlated with degree of behavioral change. To examine the role of TNF-alpha in these behavioral alterations, open-field behavior was compared in wild-type (WT) and TNF-R1-knockout (KO), ADX-MCMV-infected mice. TNF-R1-KO mice exhibited significantly attenuated decreases in number of rearings, number of center entries and time spent in center, but not distance moved, which correlated with plasma IL-6. Given the potential role of brain cytokines in these findings, mRNA expression of TNF-alpha, IL-1 and IL-6 was assessed in various brain regions. Although MCMV induced increases in proinflammatory cytokine mRNA throughout the brain (especially in ADX animals), no remarkable differences were found between WT and TNF-R1-KO mice. These results demonstrate that endogenous glucocorticoids restrain proinflammatory cytokine responses to viral infection and their impact on locomotor/exploratory activity. Moreover, TNF-alpha appears to mediate cytokine-induced changes in open-field behaviors, especially those believed to reflect anxiety.

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Adrenalitis and the adrenocortical response of resistant and susceptible mice to acute murine cytomegalovirus infection

Cited by 27 publications

References 26 publications

Endogenous glucocorticoids cause thymus atrophy but are protective during acute Trypanosoma cruzi infection

Endogenous glucocorticoids cause thymus atrophy but are protective during acute Trypanosoma cruzi infection

Role of the hypothalamic-pituitary-adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products

Endogenous glucocorticoids protect against TNF-alpha-induced increases in anxiety-like behavior in virally infected mice

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