The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions

McEwen, Bruce S.; Biron, Christine A.; Brunson, Kenneth W.; Bulloch, Karen; Chambers, William H.; Dhabhar, Firdaus S.; Goldfarb, Ronald H.; Kitson, Richard P.; Miller, Andrew H.; Spencer, Robert L.; Weiss, Jay M.

doi:10.1016/s0165-0173(96)00012-4

Cited by 745 publications

(503 citation statements)

References 320 publications

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“…These data are consistent with our previous results showing that 24-96 h of treatment with desipramine induces a 10-25% reduction in cytosolic GR binding in L929 cells; this reduction is still present after the cells have recovered for 24 h in media with no desipramine (Pariante et al, 1997). Since 24 h desipramine also induces activation and translocation of the GR from the cytoplasm to the nucleus (Pariante et al, 1997), and this is associated with a decrease of GR in the cytosolic fraction (McEwen et al, 1997), we had interpreted the desipramine-induced decrease in GR binding as representing a greater proportion of GR in the nucleus (Pariante et al, 1997). However, in the light of the present data, these results can be interpreted as an overall decrease in the total number of GRs.…”

Section: Discussionsupporting

confidence: 93%

“…One explanation for the HPA axis hyperactivity is an impaired feedback inhibition by the endogenous glucocorticoid cortisol. This feedback is mediated by the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) in the brain (McEwen et al, 1997). Patients with major depression exhibit impaired HPA negative feedback in the context of elevated circulating levels of cortisol (Nemeroff, 1996), and the GR is important in the regulation of the HPA when endogenous levels of cortisol are high .…”

Section: Introductionmentioning

confidence: 99%

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The Antidepressant Clomipramine Regulates Cortisol Intracellular Concentrations and Glucocorticoid Receptor Expression in Fibroblasts and Rat Primary Neurones

Pariante

Hye

Williamson

et al. 2003

Neuropsychopharmacol

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Incubation of LMCAT fibroblasts cells with antidepressants potentiates glucocorticoid receptor (GR)-mediated gene transcription in the presence of cortisol, but not of corticosterone. We have suggested that antidepressants do so by inhibiting the LMCAT cells membrane steroid transporter and thus by increasing cortisol intracellular concentrations. We now confirm and extend this model to primary neuronal cultures. Clomipramine, a tricyclic antidepressant, increased the intracellular accumulation of 3 H-cortisol, but not 3 Hcorticosterone, in LMCAT cells (+80%) and primary rat neurones (+20%). The latter finding is the first demonstration that a membrane steroid transporter is present in neurones. Moreover, verapamil, a membrane steroid transporter inhibitor, reduced the effects of clomipramine on the intracellular accumulation of 3 H-cortisol in LMCAT cells. Finally, clomipramine also decreased GR expression (whole-cell Western blot) in LMCAT cells (50% reduction) and primary rat neurones (80% reduction). This GR downregulation can explain the reduced GR-mediated gene transcription previously described under experimental conditions that do not elicit the effects on the LMCAT cells steroid transporter. This work further supports the hypothesis that membrane steroid transporters regulating the access of glucocorticoids to the brain in vivo are a fundamental target for antidepressant action.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

The Antidepressant Clomipramine Regulates Cortisol Intracellular Concentrations and Glucocorticoid Receptor Expression in Fibroblasts and Rat Primary Neurones

Pariante

Hye

Williamson

et al. 2003

Neuropsychopharmacol

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“…Roulin 2004b; Griffith et al 2006). The fact that glucocorticoid suppression of immune function has been observed throughout various vertebrate taxa (McEwen et al 1997;Weyts et al 1999) provide a likely proximate link between eumelanin colouration and disease resistance which so far has received little attention. On an applied level, there are some potentially important implications of this trait correlation in fishes.…”

Section: Discussionmentioning

confidence: 99%

Melanin-based skin spots reflect stress responsiveness in salmonid fish

Kittilsen

Schjolden

Beitnes-Johansen

et al. 2009

Hormones and Behavior

134

122

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This version available http://nora.nerc.ac.uk/7671/ NERC has developed NORA to enable users to access research outputs wholly or partially funded by NERC. Copyright and other rights for material on this site are retained by the authors and/or other rights owners. Users should read the terms and conditions of use of this material at http://nora.nerc.ac.uk/policies.html#access This document is the author's final manuscript version of the journal article, incorporating any revisions agreed during the peer review process. Some differences between this and the publisher's version remain. You are advised to consult the publisher's version if you wish to cite from this article. www.elsevier.comContact CEH NORA team at nora@ceh.ac.ukThe NERC and CEH trade marks and logos ('the Trademarks') are registered trademarks of NERC in the UK and other countries, and may not be used without the prior written consent of the Trademark owner. Wilson et al. 1994;Réale et al. 2007). Notwithstanding a certain lack of consensus in terminology, the evolution of these analogues of human personality has evoked considerable scientific interest. Among the questions raised are by which mechanisms behavioural syndromes are inherited, how the variation is maintained, which circumstances benefit different complex phenotypes, and what are the costs and benefits of limited plasticity imposed by more or less fixed trait associations (DeWitt et al. 1998;Koolhaas et al. 1999;Sih et al. 2004; Dingemanse and Réale 2005;McElreath et al. 2007;Réale et al. 2007;Wolf et al. 2007). Furthermore, in the barn owl (Tyto Alba) melanin-based colouration is associated with several behavioural, morphological and physiological characteristics that have been linked to stress coping ability (Almasi et al. 2008).Based on observations that HR and LR trout differed in melanin pigmentation our hypothesis was that spotted fish, in the closely related specie Atlantic salmon (Salmo Salar), 5 would show a lower cortisol reponse to stress when compared to a non-spotted group of individuals. Furthermore, several documented changes in the behaviour of the two trout lines made us predict that also behaviour would differ between groups of spotted and non-spotted fish. The main focus of this study was therefore to test the hypothesis that there exist an association between melanin-based pigmentation and hypothalamus-pituitary-interrenal (HPIaxis) reactivity in salmonid fish. Furthermore, we tested the prediction that behavioural differences are present in two groups of fish chosen divergently on melanin pigmentation. Materials and methods Quantification of melanin-based colorationIn the studies described below, photographs of experimental fish were captured with a Canon EOS 450D digital camera and transferred to a computer for further analyses of melanin-based coloration. Prior to photography, each fish were sedated in 200 mg/l MS-222 and placed adjacent to a measuring tape with millimetre resolution, allowing for an accurate estimation of the area where spots were counted. The d...

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“…The increased numbers of neutrophils observed 24 h after vaccination may be explained by the induction of IL-1 and TNF-a, which are known to trigger a release of neutrophils from the bone marrow. Moreover, type I interferon leads to redistribution of lymphocytes into the lymphatic system [25].…”

Section: Discussionmentioning

confidence: 99%

A therapeutic vaccine for nicotine dependence: preclinical efficacy, and phase I safety and immunogenicity

Maurer¹,

Jennings²,

Willers³

et al. 2005

Eur. J. Immunol.

259

198

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Nicotine is the principal addictive component in tobacco, and following uptake acts in the central nervous system. The smoking-cessation efforts of most smokers fail because a single slip often delivers sufficient nicotine to the brain to reinstate the drug-seeking behaviour. Blocking nicotine from entering the brain by induction of specific antibodies may be an effective means to prevent such relapses. The hapten nicotine was coupled to virus-like particles (VLP) formed by the coat protein of the bacteriophage Qb. In preclinical experiments, this Nicotine-Qb VLP (NicQb) vaccine induced strong antibody responses. After intravenous nicotine challenge, vaccinated mice exhibited strongly reduced nicotine levels in the brain compared with control mice. In a phase I study, 32 healthy non-smokers were immunized with NicQb. The vaccine was safe and welltolerated. All volunteers who received NicQb showed nicotine-specific IgM antibodies at day 7 and nicotine-specific IgG antibodies at day 14. Antibody levels could be boosted by a second injection or the addition of Alum as an adjuvant and the antibodies had a high affinity for nicotine. These data suggest that antibodies induced by NicQb may prevent relapses by sequestering nicotine in the blood of immunized smokers.

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The role of adrenocorticoids as modulators of immune function in health and disease: neural, endocrine and immune interactions

Cited by 745 publications

References 320 publications

The Antidepressant Clomipramine Regulates Cortisol Intracellular Concentrations and Glucocorticoid Receptor Expression in Fibroblasts and Rat Primary Neurones

The Antidepressant Clomipramine Regulates Cortisol Intracellular Concentrations and Glucocorticoid Receptor Expression in Fibroblasts and Rat Primary Neurones

Melanin-based skin spots reflect stress responsiveness in salmonid fish

A therapeutic vaccine for nicotine dependence: preclinical efficacy, and phase I safety and immunogenicity

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