Activation of Immune Function by Dehydroepiandrosterone (DHEA) in Age-Advanced Men

Khorram, Omid; Vu, Lan Phuong; Yen, S. S. C.

doi:10.1093/gerona/52a.1.m1

Cited by 142 publications

(90 citation statements)

References 41 publications

(36 reference statements)

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“…When aged individuals, being it experimental animals (36±38) or humans (39) are administered DHEA, their immune function has been claimed to be restored; they become more resistant to infections, their secretion of T cell cytokines (e.g. IL-2) is enhanced, whereas monocyte numbers are increased.…”

Section: Discussionmentioning

confidence: 99%

Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells

Canning

Grotenhuis

Wit

et al. 2000

European Journal of Endocrinology

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Background: Dehydroepiandrosterone (DHEA) has been suggested as an immunostimulating steroid hormone, of which the effects on the development of dendritic cells (DC) are unknown. The effects of DHEA often oppose those of the other adrenal glucocorticoid, cortisol. Glucocorticoids (GC) are known to suppress the immune response at different levels and have recently been shown to modulate the development of DC, thereby influencing the initiation of the immune response. Variations in the duration of exposure to, and doses of, GC (particularly dexamethasone (DEX)) however, have resulted in conflicting effects on DC development. Aim: In this study, we describe the effects of a continuous high level of exposure to the adrenal steroid DHEA (10 26 M) on the generation of immature DC from monocytes, as well as the effects of the opposing steroid DEX on this development. Results: The continuous presence of DHEA (10 26 M) in GM-CSF/IL-4-induced monocyte-derived DC cultures resulted in immature DC with a morphology and functional capabilities similar to those of typical immature DC (T cell stimulation, IL-12/IL-10 production), but with a slightly altered phenotype of increased CD80 and decreased CD43 expression (markers of maturity).The continuous presence of DEX at a concentration of 10 26 M in the monocyte/DC cultures resulted in the generation of plastic-adherent macrophage-like cells in place of typical immature DC, with increased CD14 expression, but decreased expression of the typical DC markers CD1a, CD40 and CD80. These cells were strongly reactive to acid phosphatase, but equally capable of stimulating T cell proliferation as immature DC. The production of IL-12 by these macrophage-like cells was virtually shut down, whereas the production of IL-10 was significantly higher than that of control immature DC. Conclusion:The continuous presence of a high level of GC during the generation of immature DC from monocytes can modulate this development away from DC towards a macrophage-like cell. The combination of a low CD80 expression and a shutdown of IL-12 production suggests the possibility of DEX-generated cells initiating a Th2-biased response. These effects by DEX on DC development contrast with those by DHEA, which resulted in a more typical DC although possessing a phenotype possibly indicating a more mature state of the cell.

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Section: Discussionmentioning

confidence: 99%

Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells

Canning

Grotenhuis

Wit

et al. 2000

European Journal of Endocrinology

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“…Moreover, dehydroepiandrosterone sulfate (DHEAS) has been proposed for the treatment of systemic lupus erythematosus (33). It is well known that DHEAS exerts multiple immune functions (34,35) also enhancing NKCC via local production of the immunoregulatory peptide insulin-like growth factor I (36,37).…”

Section: Introductionmentioning

confidence: 99%

Defect of a subpopulation of natural killer immune cells in Graves’ disease and Hashimoto’s thyroiditis: normalizing effect of dehydroepiandrosterone sulfate

Solerte

Precerutti²,

Gazzaruso³

et al. 2005

eur j endocrinol

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Background: The study of the natural killer (NK) immune compartment could provide important findings to help in the understanding of some of the pathogenetic mechanisms related to autoimmune thyroid diseases (Graves' disease (GD) and Hashimoto's thyroiditis (HT)). Within this context, it was suggested that alterations in NK cell cytotoxicity (NKCC) and NK production of cytokines might occur in subjects with GD and HT, whereas the normalization of NK functions could potentially contribute to the prevention of the onset or the progression of both diseases. Objective: Due to the hypothesis of alterations in NK in autoimmune thyroid diseases, we were interested to evaluate NKCC in GD and HT patients and to modulate NK function and secretory activity with cytokines and dehydroepiandrosterone sulfate (DHEAS) in an attempt to normalize NK cell defect. Design: We studied 13 patients with recent onset Graves' disease, 11 patients with Hashimoto's thyroiditis at first diagnosis and 15 age-matched healthy subjects. Methods: NK cells were concentrated at a density of 7.75 £ 10 6 cells/ml by negative immunomagnetic cell separation and validated by FACScan as CD16 þ /CD56 þ cells. NK cells were incubated with interleukin-2 (IL-2) and interferon-b (IFN-b) and co-incubated with DHEAS at different molar concentrations for measuring NKCC and the secretory pattern of tumor necrosis factor-a (TNF-a) from NK cells. Results: Lower spontaneous, IL-2-and IFN-b-modulated NKCC was demonstrated in GD and HT patients compared with healthy subjects (P , 0.001). A decrease in spontaneous and IL-2-modulated TNF-a release from NK cells was also found in both groups of patients (P , 0.001). The co-incubation of NK cells with IL-2/IFN-b þ DHEAS at different molar concentrations (from 10 28 to 10 25 M/ml/NK cells) promptly normalized NKCC and TNF-a secretion in GD and HT patients. Conclusions: A functional defect of a subpopulation of NK immune cells, involving both NKCC and the secretory activity, was demonstrated in newly-diagnosed GD and HT patients. This defect can be reversed by a dose-dependent treatment with DHEAS. The impairment of NK cell activity in autoimmune thyroid diseases could potentially determine a critical expansion of T/B-cell immune compartments leading to the generation of autoantibodies and to the pathogenesis of thyroid autoimmunity.

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“…As noted above, testosterone levels are markedly raised in women taking DHEA as a dietary supplement (Morales et al, 1994(Morales et al, , 1998Khorram et al, 1997;Casson et al, 1998). International studies report that Chinese women show lower mean testosterone concentrations than do Western women and also have a very much lower incidence of breast cancer (Key et al, 1990).…”

Section: Possible Role For Dhea In Mammary Carcinogenesismentioning

confidence: 99%

“…Serum concentrations of insulin-like growth factor 1 (IGF1) were elevated and sex hormone-binding globulin levels in the circulation were reduced in both sexes. Immune activity was activated both in men (Khorram et al, 1997) and women (Morales et al, 1998) while total body mass was increased in women but fat mass decreased in men. The increased IGF1 levels were similar for 50 mg DHEA daily for 3 months to those for 100 mg daily for 6 months (Morales et al, 1998) but no change was found in insulin concentrations.…”

Section: Introductionmentioning

confidence: 98%

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Dietary supplements of dehydroepiandrosterone in relation to breast cancer risk

Stoll

1999

Eur J Clin Nutr

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Objective: Dietary supplements of the adrernocertical hormone dehydroepiandrosterone (DHEA) are widely taken in the hope of staving off the aging process. Potential dangers have not been fully researched, particularly evidence of a correlation between increased serum concentrations of DHEA and higher breast cancer risk in postmenopausal women. Design: The review examines reports of clinical, epidemiological experimental studies for evidence that DHEA may be a factor in promoting the growth of mammary cancer. Biological mechanisms which might be involved are identi®ed. Results: DHEA is reported to inhibit the growth of human mammary cancer cells in vitro and also the growth of chemically-induced mammary cancer in rats. However, growth inhibition occurs only in the presence of high oestrogen concentrations, and growth stimulation occurs in both models in the presence of a low-level oestrogen milieu. Epidemiological studies report a positive correlation between higher serum concentrations of DHEA and increased breast cancer risk in the case of postmenopausal but not premenopausal women.Postulated mechanisms include a direct effect on mammary cells by androgenic metabolites of DHEA or an indirect effect by an increase in bioavailable oestrogen levels. The increased serum concentration of free insulinlike growth factor 1 which follows prolonged DHEA intake may also have a role by stimulating oestrogen receptor activity in breast tissue. Conclusion: Late promotion of breast cancer in postmenopausal women may be stimulated by prolonged intake of DHEA, and the risk may be increased by the endocrine abnormality associated with pre-existing abdominal obesity. Caution is advised in the use of dietary supplements of DHEA particularly by obese postmenopausal women.

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Activation of Immune Function by Dehydroepiandrosterone (DHEA) in Age-Advanced Men

Cited by 142 publications

References 41 publications

Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells

Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells

Defect of a subpopulation of natural killer immune cells in Graves’ disease and Hashimoto’s thyroiditis: normalizing effect of dehydroepiandrosterone sulfate

Dietary supplements of dehydroepiandrosterone in relation to breast cancer risk

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