In vivo and in vitro effects of glucocorticoids on lymphocyte proliferation in depression

Rupprecht, Rainer; Wodarz, Norbert; Kornhuber, Johannes; Wild, K. von; Schmitz, Brigitte; Braner, H. U.; Müller, Otto; Riederer, Peter; Beckmann, H.

doi:10.1007/bf02193752

Cited by 16 publications

(3 citation statements)

References 28 publications

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“…Although a small number of studies have investigated the functional sensitivity of PBMCs from depressed patients to the inhibitory effects of cortisol, all of them showed an increased GCs resistance as determined by in vitro or in vivo challenge with DEX (Lowy et al, 1988;Rupprecht et al, 1991b;Miller et al, 1999). In agreement with these reports, in the present study a group of untreated patients showed an expected correlation between a reduced GR number and an attenuated effect of cortisol on PHA-induced lymphocyte proliferation.…”

Section: Discussionsupporting

confidence: 90%

Characterization and functional significance of glucocorticoid receptors in patients with major depression: modulation by antidepressant treatment

Calfa

Kademian

Ceschin

et al. 2003

Psychoneuroendocrinology

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Section: Discussionsupporting

confidence: 90%

Characterization and functional significance of glucocorticoid receptors in patients with major depression: modulation by antidepressant treatment

Calfa

Kademian

Ceschin

et al. 2003

Psychoneuroendocrinology

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“…Mononuclear cells (6 x 10 6 cells) were divided into 4 groups (1.5 x 10 6 cells in each one) and stimulated with phytohemagglutinin (PHA, 5ug/ml) in RPMI 1640 supplemented with 10% fetal calf serum, 1M Hepes, 2mM/L glutamine (all from GIBCO) and 10mg/ ml gentamicine (SIGMA) in the presence of dexamethasone (10 -6 M, SIGMA), IL-2 (100 Cetus Unit), epinephrine 10 -7 M and serotonin 10 -4 M for up to 10 days in a humidified chamber with 95% air and 5% carbon dioxide. The doses of dexamethasone, epinephrine and serotonin were based on the literature 17 and previous experiment done in our laboratory and represent the increase of cortisol generated during stress and the adrenergic stress respectively 17,18 . Cells were subsequently harvested at 3 day intervals, washed and stained with the same FITC and PE conjugated monoclonal antibodies that react with the selected cell surface antigen.…”

Section: Methodsmentioning

confidence: 99%

Stress regulates the lymphocyte homing receptor CD62L (L-selectin)

Manfro

Netto

Pollack

et al. 2003

Arq. Neuro-Psiquiatr.

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-Based on a previous study showing that panic disorder patients had increased expression of naïve phenotype lymphocytes (CD45RA+ and CD62L+), increased plasma cortisol, as well as decreased interleukin-2 (IL-2) producion, we hypothesized that changes in the percentage of expression of these lymphocyte surface molecules could be related to the substances released by the hypothalamic-pituitary-adrenal (HPA) axis and possibly associated to panic disorder (cortisol, IL-2, serotonin and epinephrine). In order to study the altered expression, blood mononuclear cells of normal volunteers were stimulated with mitogen, in the presence of dexamethasone, IL-2, serotonin and epinephrin. CD62L is decreased by IL-2 in vitro. Serotonin and epinephrine did not promote changes in the expression of these surface molecules. The results of the ex vivo study are in agreement with a previous clinical study with panic patients. It could be suggested that stress is responsible for certain immunologic dysfunctions and new studies should be conducted.KEY WORDS: corticosteroids, interleukin-2, lymphocyte migration, adhesion molecules, panic disorder.Regulação do receptor de alojamento linfocitário CD62L (L Regulação do receptor de alojamento linfocitário CD62L (L Regulação do receptor de alojamento linfocitário CD62L (L Regulação do receptor de alojamento linfocitário CD62L (L Regulação do receptor de alojamento linfocitário CD62L (L-selectina) pelo estresse -selectina) pelo estresse -selectina) pelo estresse -selectina) pelo estresse -selectina) pelo estresse RESUMO -Baseado em estudo prévio que demonstrou que os pacientes com transtorno do pânico apresentavam aumento na porcentagem de expressão de linfócitos com fenótipo virgem (CD45RA+ e CD62L+), aumento no cortisol plasmático, assim como diminuição na produção de interleucinas, foi sugerido que as alterações na porcentagem de expressão dessas moléculas de superfície dos linfócitos poderia estar relacionada com a liberação de substâncias pelo eixo hipotálamo-hipófise-adrenal (HHA) e possivelmente associada ao transtorno do pânico (cortisol, IL-2, serotonina e epinefrina). Com o objetivo de estudar essas alterações, células mononucleares do sangue periférico de voluntários normais foram estimuladas com mitógeno, na presença de dexametasona, IL-2, serotonina e epinefrina. A expressão de CD62L "in vitro" é diminuida com IL-2. Serotonina e epinefrina não promovem alterações na expressão dessas moléculas de superfície. Os resultados desse estudo "in vitro" estão de acordo com o estudo clínico prévio com pacientes com transtorno do pânico. Podese sugerir que o estresse é responsável por algumas disfunções imunológicas e novos estudos devem ser delineados para testar essa hipótese.PALAVRAS-CHAVE: corticosteróides, interleucina-2, migração linfocitária, moléculas de adesão, transtorno do pânico.

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“…Of note, impaired lymphocyte sensitivity to glucocorticoids has also been observed in patients with major depression. [14, 15]. …”

Section: Introductionmentioning

confidence: 99%

Antidepressants Differentially Influence the Transcriptional Activity of the Glucocorticoid Receptor in vitro

et al. 2003

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Functional normalization of the hypothalamic-pituitary-adrenal axis in depressive patients by successful treatment with antidepressants is associated with increased efficiency of corticosteroid signal transduction. Accordingly, some antidepressants have been shown to influence the activity of the glucocorticoid receptor (GR) in cultured cells. It is not clear, however, whether this is a common principle for all antidepressants throughout all classes. Therefore, we screened a range of 18 antidepressants of different classes for their effect on GR signaling in a reporter gene assay using the mouse hippocampal cell line HT22. We evaluated GR-mediated gene transcription after short-time incubation (24 h) with different concentrations of each antidepressant (1 or 10 µM) in the presence or absence of the synthetic steroid dexamethasone (0.01 or 1 µM). The majority of antidepressants had a tendency to enhance steroid-induced GR-mediated gene transcription at high concentrations of antidepressant and low concentrations of steroid. Some antidepressants reduced the steroid-independent background activity of GR. This reduction was not due to unspecific inhibition of GR by oxidative stress, since no induction of intracellular peroxides was detectable in the concentration range of antidepressants used in our study. Furthermore, no significant change in GR activity was observed by concomitant treatment of HT22 cells with the antioxidant α-tocopherol (vitamin E). In conclusion, we report that many antidepressants enhance GR signaling in an in vitro neuronal system at clinically relevant concentrations. Those not showing an effect in vitro apparently use different mechanisms to influence GR activity that require an in vivo setting.

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In vivo and in vitro effects of glucocorticoids on lymphocyte proliferation in depression

Cited by 16 publications

References 28 publications

Characterization and functional significance of glucocorticoid receptors in patients with major depression: modulation by antidepressant treatment

Characterization and functional significance of glucocorticoid receptors in patients with major depression: modulation by antidepressant treatment

Stress regulates the lymphocyte homing receptor CD62L (L-selectin)

Antidepressants Differentially Influence the Transcriptional Activity of the Glucocorticoid Receptor in vitro

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