Regulation of adrenal glucocorticoid synthesis by interleukin-10: A preponderance of IL-10 receptor in the adrenal zona fasciculata

Koldzic-Zivanovic, Nina; Tu, Huolin; Juelich, Terry L.; Rády, Peter L.; Tyring, Stephen K.; Hudnall, S. David; Smith, Eric M.; Hughes, Thomas K.

doi:10.1016/j.bbi.2005.09.003

Cited by 37 publications

(17 citation statements)

References 43 publications

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“…This is in line with Baykal et al [56] and with those authors who show that IL-10 knock-out mice (IL-10 -/-) can be tolerized by LPS [54]. However, we cannot discard a possible role for IL-10, as redundant mechanisms in the regulation of endotoxin tolerance could be possible, although it has been shown that this anti-inflammatory cytokine regulates GC synthesis in a negative manner through the inhibition of adrenocorticotrophic hormone (ACTH) effects [57,58].…”

Section: Discussionmentioning

confidence: 85%

Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance

Rearte

Landoni

Laborde

et al. 2009

Clinical and Experimental Immunology

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SummaryGram-negative infections can result in endotoxic shock, which is the most common cause of death in intensive care units. Most of the undesirable effects in sepsis and septic shock have been ascribed to lipopolysaccharide (LPS), a normal constituent of the bacterial wall. The response to LPS involves rapid secretion of proinflammatory cytokines [tumour necrosis factor-a, interleukin (IL)-1, IL-6, IL-8, interferon-g] and the concomitant induction of antiinflammatory mediators such as IL-10 and transforming growth factor-b and glucocorticoids (GC), which render the host temporarily refractory to subsequent lethal doses of LPS challenge in a process known as LPS or endotoxin tolerance. Although protective from the development of sepsis or systemic inflammation, endotoxin tolerance has also been pointed out as the principal cause of the non-specific immunosuppression described in these patients. In this report we demonstrate, using a mouse model, that while the maintenance of tolerance is dependent upon GC, the establishment of tolerance by LPS could be inhibited by dexamethasone (Dex), a synthetic GC. Conversely, we demonstrated that mifepristone (RU486), a known GC receptor antagonist, was capable of inducing a transient and reversible disruption of endotoxin tolerance, also permitting partial restoration of the humoral immune response in LPS tolerant/immunosuppressed mice. These results are encouraging for the management of immunosuppression in sepsis and/or noninfectious shock, and deserve further investigation in the future.

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Section: Discussionmentioning

confidence: 85%

Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance

Rearte

Landoni

Laborde

et al. 2009

Clinical and Experimental Immunology

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“…IL-10-deficient mice develop autoimmune disease and chronic inflammation (Kuhn et al, 1993; Rennick et al, 1995), but effects of glucocorticoids in these mice have not been reported. However, IL-10 has been implicated in negative regulation of corticosterone synthesis, acting at the adrenal gland (Koldzic-Zivanovic et al, 2006), providing a plausible homeostatic mechanism to terminate HPA axis activation once inflammation is resolving. Like IL-10, administration of AnxA1 can mimic a subset of the effects of glucocorticoids (although in T cells, AnxA1 effects may be opposite to those of glucocorticoids) (Perretti and D’Acquisto, 2009).…”

Section: The Repressive Actions Of Glucocorticoidsmentioning

confidence: 99%

The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights

Coutinho

Chapman

2011

Molecular and Cellular Endocrinology

1,430

952

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Since the discovery of glucocorticoids in the 1940s and the recognition of their anti-inflammatory effects, they have been amongst the most widely used and effective treatments to control inflammatory and autoimmune diseases. However, their clinical efficacy is compromised by the metabolic effects of long-term treatment, which include osteoporosis, hypertension, dyslipidaemia and insulin resistance/type 2 diabetes mellitus. In recent years, a great deal of effort has been invested in identifying compounds that separate the beneficial anti-inflammatory effects from the adverse metabolic effects of glucocorticoids, with limited effect. It is clear that for these efforts to be effective, a greater understanding is required of the mechanisms by which glucocorticoids exert their anti-inflammatory and immunosuppressive actions. Recent research is shedding new light on some of these mechanisms and has produced some surprising new findings. Some of these recent developments are reviewed here.

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“…Fluctuations in anti-inflammatory IL-10 are similarly associated with depressive symptoms in humans and are proposed to influence depressive behavior when reduced anti-inflammatory expression is unable to counterbalance the expression of pro-inflammatory cytokines [17], [18]. Additionally, IL-10 plays a role in regulating hypothalamic-pituitary-adrenal (HPA) axis homeostasis by suppressing adrenocorticotropic hormone-induced steroid production and diminished IL-10 expression can affect HPA hyperactivity and glucocorticoid resistance seen in depressed patients [19]–[22]. Importantly, IL-10 treatment ameliorates LPS-induced sickness behavior and depressive symptoms in transgenic mice [23]–[25].…”

Section: Introductionmentioning

confidence: 99%

Prolonged Restraint Stress Increases IL-6, Reduces IL-10, and Causes Persistent Depressive-Like Behavior That Is Reversed by Recombinant IL-10

et al. 2013

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Altered inflammatory cytokine profiles are often observed in individuals suffering from major depression. Recent clinical work reports on elevated IL-6 and decreased IL-10 in depression. Elevated IL-6 has served as a consistent biomarker of depression and IL-10 is proposed to influence depressive behavior through its ability to counterbalance pro-inflammatory cytokine expression. Clinical and animal studies suggest a role for IL-10 in modifying depressive behavior. Murine restraint stress (RST) is regularly employed in the study of behavioral and biological symptoms associated with depressive disorders. While responses to acute RST exposure have been widely characterized, few studies have examined the ongoing and longitudinal effects of extended RST and fewer still have examined the lasting impact during the post-stress period. Consistent with clinical data, we report that a protocol of prolonged murine RST produced altered cytokine profiles similar to those observed in major depressive disorder. Parallel to these changes in circulating cytokines, IL-10 mRNA expression was diminished in the cortex and hippocampus throughout the stress period and following cessation of RST. Moreover, chronic RST promoted depressive-like behavior throughout the 28-day stress period and these depressive-like complications were maintained weeks after cessation of RST. Because of the correlation between IL-10 suppression and depressive behavior and because many successful antidepressant therapies yield increases in IL-10, we examined the effects of IL-10 treatment on RST-induced behavioral changes. Behavioral deficits induced by RST were reversed by exogenous administration of recombinant IL-10. This work provides one of the first reports describing the biological and behavioral impact following prolonged RST and, taken together, this study provides details on the correlation between responses to chronic RST and those seen in depressive disorders.

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Regulation of adrenal glucocorticoid synthesis by interleukin-10: A preponderance of IL-10 receptor in the adrenal zona fasciculata

Cited by 37 publications

References 43 publications

Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance

Differential effects of glucocorticoids in the establishment and maintenance of endotoxin tolerance

The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights

Prolonged Restraint Stress Increases IL-6, Reduces IL-10, and Causes Persistent Depressive-Like Behavior That Is Reversed by Recombinant IL-10

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