Platinum nanoflowers with peroxidase-like property in a dual immunoassay for dehydroepiandrosterone.

Platinum nanoflowers (PtNFs) were utilized in a competitive enzyme-linked immunosorbent assay (ELISA) and in a lateral flow immunoassay (LFIA) for superior peroxidase-like activity and intense brown color, respectively. PtNFs were linked to the polyclonal antibody (pAb) to form the pAb-PtNFs probes for the dual immunoassay. Based on optimized pAb-PtNF probes, both enzyme-linked immunosorbent assay (PtNFs-ELISA) and lateral flow immunoassay (PtNFs-LFIA) perform very well. The absorbance at 450 nm decreases linearly in the DHEA concentration range 2.1 to 118.1 ng mL-1, and the limit of detection is 1.3 ng mL-1 and the IC50 value is 15.7 ng mL-1 of PtNFs-ELISA. The visual cut-off value of PtNFs-LFIA is 10.0 ng mL-1. The average recoveries from spiked samples range from 95.0 to 108.9% with a coefficient of variation below 12.2%. Excellent recoveries and correlation between the two methods were observed. Furthermore, the designed immunosensors exhibited good selectivity, confirming a broad development prospect in DHEA monitoring. Graphical Abstract.

7-oxo-DHEA enhances impaired M. tuberculosis-specific T cell responses during HIV-TB coinfection.

BACKGROUND: Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), affecting approximately one third of the world's population. Development of an adequate immune response will determine disease progression or progress to chronic infection. Risk of developing TB among human immunodeficiency virus (HIV)-coinfected patients (HIV-TB) is 20-30 times higher than those without HIV infection, and a synergistic interplay between these two pathogens accelerates the decline in immunological functions. TB treatment in HIV-TB coinfected persons is challenging and it has a prolonged duration, mainly due to the immune system failure to provide an adequate support for the therapy. Therefore, we aimed to study the role of the hormone 7-oxo-dehydroepiandrosterone (7-OD) as a modulator of anti-tuberculosis immune responses in the context of HIV-TB coinfection. METHODS: A cross-sectional study was conducted among HIV-TB patients and healthy donors (HD). We characterized the ex vivo phenotype of CD4 + T cells and also evaluated in vitro antigen-specific responses by Mtb stimulation of peripheral blood mononuclear cells (PBMCs) in the presence or absence of 7-OD. We assessed lymphoproliferative activity, cytokine production and master transcription factor profiles. RESULTS: Our results show that HIV-TB patients were not able to generate successful anti-tubercular responses in vitro compared to HD, as reduced IFN-γ/IL-10 and IFN-γ/IL-17A ratios were observed. Interestingly, treatment with 7-OD enhanced Th1 responses by increasing Mtb-induced proliferation and the production of IFN-γ and TNF-α over IL-10 levels. Additionally, in vitro Mtb stimulation augmented the frequency of cells with a regulatory phenotype, while 7-OD reduced the proportion of these subsets and induced an increase in CD4 + T-bet+ (Th1) subpopulation, which is associated with clinical data linked to an improved disease outcome. CONCLUSIONS: We conclude that 7-OD modifies the cytokine balance and the phenotype of CD4 + T cells towards a more favorable profile for mycobacteria control. These results provide new data to delineate novel treatment approaches as co-adjuvant for the treatment of TB.

Effect of dehydroepiandrosterone on the immune function of mice in vivo and in vitro.

Dehydroepiandrosterone (DHEA) has anti-inflammatory, anti-oxidant and immune-regulating properties, while the mechanism of DHEA actions remains unclear. The present study aims to investigate the effect and possible mechanism of DHEA on immune function of mice in vivo and in vitro. In vivo, a lipopolysaccharide (LPS)-induced experimental inflammation model was constructed to analyze the regulation of DHEA on anti-oxidative and immune function in ICR mice; In vitro, the effects of DHEA on the biological functions of lymphocytes and macrophages were studied. The results showed that DHEA increased the activity of total antioxidant capacity and superoxide dismutase, while it decreased the level of reactive oxygen species in LPS-induced mice. Meanwhile, DHEA increased the proportion of T lymphocytes and decreased that of B lymphocytes in primary cultured spleen lymphocytes, and markedly enhanced the Th1/Th2 ratio in spleen T lymphocytes. Furthermore, DHEA significantly increased the Th1 type cytokine (IL-2 and IFN-α) and decreased the Th2 type cytokine (IL-4 and IL-10) levels in LPS-induced mice or in primary cultured spleen T lymphocytes. In addition, DHEA improved the phagocytic ability, enhanced the NO production and increased the iNOS activity in peritoneal macrophages. Our data indicates that DHEA increases the macrophages function via improving NO content and up-regulating TNF-α expression levels; and it evoked a Th1 immuno-response and repressed a Th2 immuno-response through promoting a shift in Th1/Th2 balance toward Th1-dominant immunity in vivo and in vitro. These results provide substantial evidence on the mechanism of DHEA-mediated immune function and the efficient protection against infectious and inflammatory response in animals and humans.

Androgens and innate immunity in rehabilitated semi-captive orangutans (Pongo pygmaeus morio) from Malaysian Borneo.

Despite the implications for the development of life-history traits, endocrine-immune trade-offs in apes are not well studied. This is due, in part, to difficulty in sampling wild primates, and lack of methods available for immune measures using samples collected noninvasively. Evidence for androgen-mediated immune trade-offs in orangutans is virtually absent, and very little is known regarding their pattern of adrenal development and production of adrenal androgens. To remedy both of these deficiencies, sera were collected from orangutans (Pongo pygmaeus morio) (N = 38) at the Sepilok Orangutan Rehabilitation Centre, Sabah, Malaysia, during routine health screenings. Testosterone, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone-sulfate (DHEA-S) were assayed, along with two measures of functional innate immunity. DHEA-S concentrations, but not DHEA, increased with age in this sample of 1-18 year old animals. DHEA concentrations were higher in animals with higher levels of serum bacteria killing ability, while DHEA-S and testosterone concentrations were higher in animals with reduced complement protein activity. Patterns of DHEA-S concentration in this sample are consistent with patterns of adrenarche observed in other apes. Results from this study suggest that in addition to testosterone, DHEA and DHEA-S may have potent effects on immunological activity in this species.

Adverse neuro-immune-endocrine interactions in patients with active tuberculosis.

The nervous, endocrine and immune systems play a crucial role in maintaining homeostasis and interact with each other for a successful defensive strategy against injurious agents. However, the situation is different in long-term diseases with marked inflammation, in which defensive mechanisms become altered. In the case of tuberculosis (TB), this is highlighted by several facts: an imbalance of plasma immune and endocrine mediators, that results in an adverse environment for mounting an adequate response against mycobacteria and controlling inflammation; the demonstration that dehidroepiandrosterone (DHEA) secretion by a human adrenal cell line can be inhibited by culture supernatants from Mycobacterium tuberculosis-stimulated peripheral blood mononuclear cells - PBMC - of TB patients, with this effect being partly reverted when neutralizing transforming growth factor-ß in such supernantants; the in vitro effects of adrenal steroids on the specific immune response of PBMC from TB patients, that is a cortisol inhibition of mycobacterial antigen-driven lymphoproliferation and interferon-γ production as well as a suppression of TGF-ß production in DHEA-treated PBMC; and lastly the demonstration that immune and endocrine compounds participating in the regulation of energy sources and immune activity correlated with the consumption state of TB patients. Collectively, immune-endocrine disturbances of TB patients are involved in critical components of disease pathology with implications in the impaired clinical status and unfavorable disease outcome. This article is part of a Special Issue entitled 'Neuroinflammation in neurodegeneration and neurodysfunction'.

Influence of different length linker containing DHEA-7-cmo-enzyme conjugates on sensitivity and specificity of DHEA-3-hs-antibody.

The introduction of spacers in coating steroid antigen or enzyme conjugates or immunogen is known to exert an influence on the sensitivity of steroid enzyme immunoassays. We have introduced different homobifunctional spacers having varying atomic length (3 to 10) between enzyme and dehydroepiandrosterone (DHEA) moiety and studied their effects on functional parameters such as sensitivity and specificity of DHEA enzyme immunoassays. DHEA-3-hemisuccinate-bovine serum albumin (DHEA-3-HS-BSA) was used as immunogen to raise the antiserum in New Zealand white rabbits. Five enzyme conjugates were prepared using DHEA-7-carboxymethyloxime (DHEA-7-CMO) as carboxylic derivative of DHEA and horseradish peroxidase (HRP) as an enzyme label. These were DHEA-7-CMO-HRP, DHEA-7-CMO-urea-HRP (DHEA-7-CMO-U-HRP), DHEA-7-CMO-ehylenediamine-HRP (DHEA-7-CMO-EDA-HRP), DHEA-7-CMO-carbohydrazide-HRP (DHEA-7-CMO-CH-HRP), and DHEA-7-CMO-adipic acid dihydrazide-HRP (DHEA-7-CMO-ADH-HRP). The influence of different atomic length linkers on sensitivity and specificity were studied with reference to label without linker. The results of the present investigation revealed that DHEA moiety having a 3-hemisuccinate carboxyl arm that is hydrophilic in nature and spacer arm urea that is also hydrophilic in nature when used for the link to the protein carrier and enzyme for the preparation of immunogen and enzyme conjugate respectively resulted in development of assay having comparable sensitivity and lowest ED(50) as compared to other spacers. Thus sensitivity and ED(50) of the assay depend partly on the nature of the steroid and spacer arm link to the carrier protein and the enzyme.

Influence of different length linker containing DHEA-7-CMO-enzyme conjugates on sensitivity and specificity of DHEA-17-CMO-antibody.

Introduction of spacers in enzyme conjugates is known to exert an influence on the assay parameters of steroid enzyme immunoassays. We have introduced 3 to 10 atomic length linkers between enzyme and steroid moieties and studied their effects on sensitivity and specificity of dehydroepiandrosterone enzyme immunoassays. Dehydroepiandrosterone-17-carboxymethyloxime-bovine serum albumin (DHEA-17-CMO-BSA) was used as an immunogen to raise the antiserum in New Zealand white rabbits. Five enzyme conjugates were prepared using DHEA-7-CMO as carboxylic derivative of DHEA and horseradish peroxidase (HRP) as label. These were DHEA-7-CMO-HRP, DHEA-7-CMO-urea-HRP (DHEA-7-CMO-U-HRP), DHEA-7-CMO-ehylenediamine-HRP (DHEA-7-CMO-EDA-HRP), DHEA-7-CMO-carbohydrazide-HRP (DHEA-7-CMO-CH-HRP), and DHEA-7-CMO-adipic acid dihydrazide-HRP (DHEA-7-CMO-ADH-HRP). The influence of different atomic length linkers on sensitivity and specificity were studied with reference to label without linker. The results of the present investigation revealed that with incorporation of linkers, the sensitivity improves, whereas specificity only marginally improves. These differential behaviors of various linkers toward the sensitivity and specificity of assays might be due to the difference in the magnitude of overall forces of attraction between the antibody and the enzyme conjugates.

Antigen heterologous enzyme linked immunosorbent assay for the measurement of DHEA in serum.

Homologous and heterologous combinations of enzyme conjugate and antibody in steroid enzyme immunoassay (EIA) influences unlabeled steroid recognition by antibody that affects sensitivity of the assay. To develop dehydroepiandrosterone (DHEA) antigen heterologous enzyme linked immunosorbent assay (ELISA), antibodies were generated against DHEA-3-hemisuccinate-bovine serum albumin (DHEA-3-HS-BSA), DHEA-7-carboxymethyloxime-bovine serum albumin (DHEA-7-CMO-BSA), and DHEA-17-carboxymethyloxime-bovine serum albumin (DHEA-17-CMO-BSA). Five horseradish peroxidase (HRP) enzyme conjugates were prepared using five testosterone derivatives [testosterone-3-CMO (T-3-CMO), testosterone-17-HS (T-17-HS), testosterone-17-glucuronoside (T-17-G), testosterone-19-carboxymethylether (T-19-CME), and testosterone-11-HS (T-11-HS)]. Fifteen antigen heterologous combinations of antibody and enzyme conjugates were evaluated in the standard binding assay; only two combinations showed binding. The use of antigen heterologous combination (different antigen in label than the immunogen) resulted in development of a simple, direct, and convenient assay as it permits the direct addition of the serum sample into the assay and it requires only 1.5 h to complete.

Influence of different homologous and heterologous combinations of antibodies and enzyme conjugates of dehydroepiandrostosterone on the sensitivity and specificity of DHEA ELISA.

Anti-sera were raised against three immunogen: dehydroepiandrostosterone-17-carboxymethyl-oxime-bovine serum albumin (DHEA-17-CMO-BSA), DHEA-7-CMO-BSA, and dehydroepiandrostosterone-3-hemisuccinate-bovine serum albumin (DHEA-3-HS-BSA). They were evaluated with horseradish peroxidase (HRP)-labeled DHEA-17-CMO, DHEA-7-CMO, DHEA-3-HS enzyme conjugates for their influence on the sensitivity and specificity of ELISA. Of the various combinations, DHEA-3-HS-BSA antiserum along with DHEA-7-CMO-horseradish peroxidase (DHEA-7-CMO-HRP) enzyme conjugate showed no cross-reaction with any of the closely related steroids. All the homologous combinations appeared to be less sensitive due to their low affinity for dehydroepiandrostosterone. Out of six heterologous systems tested, only three combinations, (1) anti-DHEA-17-CMO antiserum and DHEA-7-CMO-horseradish peroxidase, (2) anti-DHEA-7-CMO-antiserum and DHEA-3-HS-horseradish peroxidase, and (2) anti-DHEA-3-HS-antiserum and DHEA-7-CMO-horseradish peroxidase, showed displacement. The former two assays were less specific; the first one showed 15.38% and 16.66% cross-reaction with androstenediol and testosterone, respectively, whereas the second assay showed 30.3%, 22.72%, 111.1%, 62.5%, and 31.25% cross-reaction with DHEA-glucuronide, 16-dihydroxyprogesterone, androstenediol, etiocholon-3-ß-ol-17-one, and aldosterone, respectively. The ability of DHEA to displace the DHEA-enzyme conjugate and the specificity of the assay appear to depend on the position of the enzyme label on the DHEA molecule as well as on the availability of antigenic sites in particular combinations of antibody and DHEA-enzyme conjugates.

Does dehydroepiandrosterone influence the expression of urticaria?-a mini review.

Chronic urticaria is a challenging problem since the exact cause and mechanism involved in the disease development have still remained unknown. This disease is associated with mast cells activation and immunoinflammatory processes. Interestingly, dysfunctions of the neuroendocrine-immune system due to stress and other factors seem to appear as a very interesting theory for urticaria pathogenesis. Dehydroepiandrosterone and its sulfate derivative (DHEA-S) appear to have regulatory effects in immune homeostasis and are regulated by the nervous system, and it is suggested that they may be an integral element of neuroimmunomodulation. Our studies showed substantially decreased serum concentration of DHEA-S in patients with chronic urticaria. However, current knowledge prevents answering whether lower circulating DHEA-S concentration is a primary phenomenon or just an accompanying one which appears as a response of different systems to the course of the illness and may not be of any importance for the pathogenesis of urticaria whatsoever. This review is a summary of clinical research on the role of DHEA in chronic urticaria.

Dehydroepiandrosterone as a regulator of immune cell function.

Dehydroepiandrosterone (DHEA) is a C19 steroid of adrenal origin. Notably, its secretion declines with age, a phenomenon referred to as the "adrenopause". For many years, the physiological significance of DHEA remained elusive. However, many studies have now shown that DHEA has significant immune modulatory function, exhibiting both immune stimulatory and anti-glucocorticoid effects. Although several of these studies are limited by the fact that they were carried out in rodents, who are incapable of adrenal DHEA production, and therefore have very low circulating levels of this steroid, evidence from the study of immune cells is now accumulating to suggest a role for DHEA in regulating human immunity. This ability to regulate immune function has raised interest in the therapeutic potential of DHEA as a treatment for the immunological abnormalities that arise in subjects with low circulating levels of this hormone. This has included attempts at reversing the impaired immune response of older individuals to vaccination and restoring immune regulation in patients with chronic autoimmune disease. This review summarises the reported effects of DHEA on immune function and discusses the therapeutic potential of this steroid in geriatric medicine and particularly in age-related disease with an immune component.

Fecal dehydroepiandrosterone (DHEA) immunoreactivity as a noninvasive index of circulating DHEA activity in young male laboratory rats.

Evidence suggests that dehydroepiandrosterone (DHEA) plays a key role in stress and coping responses. Fecal sampling permits assessment of hormone-behavior interactions reliably and effectively, but no previous study has compared circadian- or stress-dependent alterations between serum DHEA and its fecal metabolites. In the current study, young (28 d of age) male rats were assigned to either an experimental (n = 6) or control (n = 6) group. Rats in the experimental group were exposed to a forced swim test to assess their behavioral and physiologic response to an environmental stressor; blood samples were drawn before the test (baseline), immediately after the test, and at 2 later time points. Only fecal samples were collected from control animals. Fecal DHEA and corticosterone metabolites were monitored in all animals for 24 h. DHEA metabolites in control rats exhibited significant diurnal variation, showing a similar temporal pattern as that of corticosterone metabolites. In addition, fecal and serum DHEA levels were highly correlated. Significant peaks in both DHEA and corticosterone metabolite levels were detected. These data suggest that measures of fecal DHEA can provide a complementary, noninvasive method of assessing adrenal gland function in rats.

Effects of combined bacille Calmette-Guérin and dehydroepiandrosterone treatment on established asthma in mice.

Both bacille Calmette-Guerin (BCG) and dehydroepiandrosterone induce Th1 immune responses and suppress Th2 allergic reactions. To investigate whether a combined administration of BCG and dehydroepiandrosterone treat asthma more effectively, BALB/c mice (n = 8 per group) with established airway hyper-responsiveness were treated with BCG and/or dehydroepiandrosterone. Combined treatment with 2 x 10(5) colony-forming units (CFUs) of BCG and 0.01% dehydroepiandrosterone was the most effective one at suppressing eosinophilia in bronchoalveolar lavage fluids. In addition, this combination also was better at suppressing hypersensitivity as compared to BCG alone (13.7 +/- 4.0- versus 3.6 +/- 0.5-fold increase in the sensitivity index; P < .05) in male mice. Similarly, the effect of the combined treatment was superior to that of individual treatments at decreasing the serum ovalbumin-specific immunoglobulin E (IgE) level. However, the addition of 0.1% dehydroepiandrosterone to BCG significantly decreased the efficacy of BCG on hypersensitivity in female mice. In male mice, the suppressive effect of the treatments on hypersensitivity tended to be lower, and the baseline interferon-gamma /interleukin-5 (IFN-gamma /IL-5) ratio in the splenocyte supernatant was significantly higher as compared to female mice. In conclusion, treatment with an appropriate combination of BCG and dehydroepiandrosterone had additive therapeutic effects on mice with established asthma. Androgens in males and dehydroepiandrosterone overdose might reduce the efficacy of BCG.

The Th1-promoting effects of dehydroepiandrosterone can provide an explanation for the stronger Th1-immune response of women.

Estrogens foster immunological processes driven by CD4+ Th2 cells and B cells and androgens foster Th1 CD4+ and CD8+ cell activity. Higher levels of IFN-gamma and IL-2 and lower levels of IL-4 and IL-10 are detected in the phytohemagglutinin-stimulated lymphocyte culture supernatants of men compared with women. It is documented that the physiologic levels of estrogens produced during the luteal phase of the menstrual cycle shift the female immune system toward a Th2-type response and that the Th1 cytokines are increased in postmenopausal women. However, the Th1 immune response is also surprisingly stronger in women, hence affording them a better protection against infections. Nickel sensitivity, a Th1 immune reaction, seems to be more common in women even if men wear earrings. Further, not only the Th2 but also the Th1 autoimmune diseases are generally more common in women than men. How do women advance a stronger Th1 response than men? It is suggested that in contrast to the paradigm that estrogens lead to a Th2 bias, estrogens can enhance Th1 cytokine production also. However, the discrepant effects of estrogens are difficult to be reconciled from a molecular viewpoint and hence are not advocated by all authors. This paper provides an explanation: The effects of dehydroepiandrosterone on Th1/Th2 balance seem to be model-specific; in humans dehydroepiandrosterone, represents a pivotal up-regulator of Th1 immune response. Steroid sulphatase is a microsomal enzyme that cleaves the sulphate group of dehydroepiandrosterone sulphate. This enzyme is controlled by an X-linked gene that escapes the Lyon effect of X-inactivation; as a result, women usually have about twice steroid sulphatase in their cells, including macrophages, as have men. Putting all these facts together, it could be concluded that women's macrophages, which contain higher steroid sulphatase levels and enter peripheral lymphoid organs through afferent lymphatic drainage, produce higher levels of dehydroepiandrosterone in these organs; and higher levels of this hormone produce stronger Th1 immune responses.

The role of stress factors during aging of the immune system.

This manuscript reviews current evidence suggesting that aging of the immune system (immunosenescence) may be closely related to chronic stress and stress factors. Healthy aging has been associated with emotional distress in parallel to increased cortisol to dehydroepiandrosterone (DHEA) ratio. The impaired DHEA secretion together with the increase of cortisol results in an enhanced exposure of lymphoid cells to deleterious glucocorticoid actions. The lack of appropriated growth hormone signaling during immunosenescence is also discussed. It follows that altered neuroendocrine functions could be underlying several immunosenescence features. Indeed, changes in both innate and adaptive immune responses during aging are also similarly reported during chronic glucocorticoid exposure. In addition, chronically stressed elderly subjects may be particularly at risk of stress-related pathology because of further alterations in both neuroendocrine and immune systems. The accelerated senescent features induced by chronic stress include higher oxidative stress, reduced telomere length, chronic glucocorticoid exposure, thymic involution, changes in cellular trafficking, reduced cell-mediated immunity, steroid resistance, and chronic low-grade inflammation. These senescent features are related to increased morbidity and mortality among chronically stressed elderly people. Overall, these data suggest that chronic stress leads to premature aging of key allostatic systems involved in the adaptation of the organisms to environmental changes. Stress management and psychosocial support may thus promote a better quality of life for elderly people and at the same time reduce hospitalization costs.

The adrenal steroid response during tuberculosis and its effects on the mycobacterial-driven IFN-gamma production of patients and their household contacts.

Earlier studies revealed that patients with tuberculosis (TB) have imbalanced immunoendocrine responses and that adrenal steroids [cortisol and dehydroepiandrosterone (DHEA)] can modify their specific cell-mediated immune response. Because most household contacts (HHCs) of contagious TB patients develop a subclinical and self-controlled process (latent TB), we studied some features of their immune and endocrine responses, particularly those related to the hypothalamic-pituitary-adrenal axis. Nineteen HHCs, 24 untreated TB patients (15 moderate, 9 advanced), and 18 healthy controls of similar age were studied. Patients had increased and reduced levels of cortisol and DHEA, respectively. DHEA levels were also reduced in HHCs. Stimulation of peripheral blood mononuclear cells (PBMC) with Mycobacterium tuberculosis sonicate resulted in increased in vitro lymphoproliferation in HHCs, while advanced patients showed the lowest response. Significantly higher amounts of interferon (IFN)-gamma were detected in supernatants from stimulated PBMC of HHCs when compared to controls and TB patients. Addition of cortisol to the cultures inhibited mycobacterial antigen-driven IFN-gamma production in all groups, although HHC supernatant contained significantly higher concentrations. In contrast, addition of DHEA to cultures of cells from HHCs resulted in increased IFN-gamma levels. These results suggest the existence of a particular immunoendocrine relation assuring a preserved IFN-gamma production in healthy housemates of TB patients.

7-Hydroxy androstene steroids and a novel synthetic analogue with reduced side effects as a potential agent to treat autoimmune diseases.

The metabolome of dehydroepiandrosterone (DHEA), the most abundant adrenal steroid in the human body, includes androgens, estrogens and a series of immune regulating hormones that lack androgenic or estrogenic activity. Of these, 7-hydroxy derivatives, once considered physiologically inactive end products of metabolism, possess a combination of potent anti-inflammatory and immune modulating activity without androgenic or estrogenic capacity. Oxygenated metabolites derived from androstenediol (AED), the predominant precursor in rodents, may be responsible for many activities initially attributed to exogenous DHEA administered to rodents. We here review the discovery of these compounds in models of inflammation and autoimmune diseases, discuss the potential mode of action and trace the development of a specific synthetic derivative, which is less labile to metabolism and which may at last deliver to humans the benefits of DHEA observed in rodents.

Dehydroepiandrosterone in systemic lupus erythematosus.

Dehydroepiandrosterone (DHEA) is a weak androgen that exerts pleomorphic effects on the immune system. The hormone has no known receptor, and consequently, its mechanism of action on immunocompetent cells remains poorly understood. Interestingly, serum levels of DHEA are decreased in patients with inflammatory diseases including lupus, and these levels seem to correlate inversely with disease activity. Following encouraging studies demonstrating beneficial effects of DHEA supplementation in murine lupus models, several clinical studies have tested the effect of DHEA in lupus patients. DHEA treatment could improve overall quality-of-life assessment measures and glucocorticoid requirements in some lupus patients with mild to moderate disease; however, DHEA's effect on disease activity in lupus patients remains controversial. Long-term safety studies are required in light of the reported effect of DHEA supplementation in lowering high-density lipoprotein cholesterol in lupus patients.

[Current views on the role of dehydroepiandrosterone in physiology, pathology and therapy]. / Wspólczesne poglady na temat roli dehydroepiandrosteronu w fizjologii, patologii i terapii.

Dehydroepiandrosterone (DHEA) and its sulfate metabolite (DHEAS) are the major androgens secreted by the human adrenal gland. The decline in their production is the most characteristic age-related change in the adrenal cortex. This process, known as 'adrenopause' may contribute to the increased incidence of atherosclerosis, cancer, or dementia in older people. The possibility of using DHEA in management has attracted considerable attention over recent years. Whereas DHEA therapy seems to be effective in treating patients with adrenal insufficiency and systemic lupus erythematosus, clinical studies investigating the potential efficacy of DHEA therapy in multiple other disorders (Alzheimer disease, depression, cardiovascular disease, osteoporosis, sexual dysfunctions) have not provided consistent results. Further research is also needed to better assess the efficacy and safety of DHEA supplementation in patients with advanced age. This review evaluates current understanding of physiology and pathology of DHEA production and summarizes the possible therapeutic value of this hormone.

Effects of combined BCG and DHEA treatment in preventing the development of asthma.

Both BCG and dehydroepiandrosterone (DHEA) induce Th1 immune responses and suppress Th2 allergic reactions. To investigate whether the combination of BCG and DHEA has an additive effect on asthma prevention, BALB/c mice (n = 10 per group) were given an intraperitoneal injection of BCG at the beginning of sensitization, and fed mice chow containing DHEA throughout the study. In female mice, the combined administration of 2 x 10(4) CFUs BCG and 0.01% DHEA effectively suppressed the ovalbumin-induced increase in airway sensitivity to methacholine (56.5 vs. 8.2 mg/mL, p < 0.01), while BCG (13.9 mg/mL) or DHEA (17.9 mg/mL) alone did not. However, the addition of high dose (0.1%) DHEA decreased the efficacy of high dose (2 x 10(5) CFUs) BCG in suppressing the airway responsiveness and eosinophilia. In male mice, the treatments with BCG and/or DHEA were less effective, and the interferon-gamma/interleukin-4 ratio in the splenocyte supernatant was significantly higher and the ovalbumin-specific IgE concentration in the serum was significantly lower as compared to female mice. In conclusion, the combination of low doses of BCG and DHEA had an additive effect in suppressing the development of airway hypersensitivity. Androgens in males and DHEA overdose might reduce the efficacy of BCG.