Dehydroepiandrosterone, Dehydroepiandrosterone Sulfate and Related Steroids: Their Role in Inflammatory, Allergic and Immunological Disorders

Dillon, Joseph S.

doi:10.2174/1568010054022079

Cited by 106 publications

(91 citation statements)

References 144 publications

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“…Among hormonal effects on the immune response, glucocorticoids can promote a Th2 cytokine acquisition profile [14], facilitating Th2 activities, whereas its natural antagonist dehydroepiandrosterone (DHEA) is able to favor Th1 cytokine production and interfere with Th2 cytokine synthesis [15]. In fact, the synthetic DHEA derivative, 16 α-bromoepiandrosterone, exerts beneficial effects in clinical and experimental TB and in HIV patients [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

HIV–TB coinfection impairs CD8⁺ T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses

et al. 2015

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Tuberculosis (TB) is the leading cause of death among HIV-positive patients. The decreasing frequencies of terminal effector (T TE ) CD8 + T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb).We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV-TB patients. Here, we aimed to study Mtb-specific cytotoxicity, IFN-γ secretion, memory status of CD8 + T cells, and their modulation by DHEA during HIV-TB coinfection. CD8 + T cells from HIV-TB patients showed a more differentiated phenotype with diminished naïve and higher effector memory and T TE T-cell frequencies compared to healthy donors both in total and Mtb-specific CD8 + T cells. Notably, CD8 + T cells from HIV-TB patients displayed higher Terminal Effector (T TE ) CD45RA dim proportions with lower CD45RA expression levels, suggesting a not fully differentiated phenotype. Also, PD-1 expression levels on CD8 + T cells from HIV-TB patients increased although restricted to the CD27 + population. Interestingly, DHEA plasma levels positively correlated with T TE in CD8 + T cells and in vitro DHEA treatment enhanced Mtb-specific cytotoxic responses and terminal differentiation in CD8 + T cells from HIV-TB patients. Our data suggest that HIV-TB coinfection promotes a deficient CD8 + T-cell differentiation, whereas DHEA may contribute to improving antitubercular immunity by enhancing CD8 + T-cell functions during HIV-TB coinfection.Keywords: Coinfection r CD8 + T cells r Cell differentiation r DHEA r HIV r Tuberculosis Additional supporting information may be found in the online version of this article at the publisher's web-site Correspondence: Guadalupe V. Suarez e-mail: suarez_guadalupe@hotmail.com IntroductionNearly one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), the etiologic agent of tuberculosis (TB). HIV coinfection is the main risk factor for progression C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu 2530 Guadalupe V. Suarez et al. Eur. J. Immunol. 2015. 45: 2529-2541 from latent to active TB disease, increasing the risk of latent TB (LTB) reactivation up to 20-fold [1]. It is well established that CD4 + T cells are critical for resistance to Mtb [2]. Mtb infection also elicits CD8 + T-cell responses, which are recruited to the lung during infection and found in the granulomas of infected people [3]. Although it is still unknown how CD8 + T cells may mediate protection against TB, it has been suggested that while CD4 + T cells are more important in controlling bacterial replication during the acute phase of infection, CD8 + T cells play a greater role during latency, possibly via immunesurveillance of cells with higher numbers of intracellular bacilli [4,5]. Besides cytokine secretion (IFN-γ and TNF-α), CD8 + T cells can induce T-cell-mediated cytotoxicity of infected cells, the major function of these cells [6]. Also, cytotoxic CD8 + T cells are able to directly kill intracell...

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Section: Introductionmentioning

confidence: 99%

HIV–TB coinfection impairs CD8⁺ T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses

et al. 2015

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“…The HPA axis regulates the production of corticosteroids and other steroid hormones, such as dehydroepiandrosterone (DHEA), that have a variety of functions in different tissues (5,9,30). With respect to immunity, corticosteroids are generally antiinflammatory (3,20); therefore, it may be for good reason that mice with an SJL background are extensively used in experimental allergic encephalomyelitis (EAE) studies (2).…”

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confidence: 99%

Lethal Silver-Haired Bat Rabies Virus Infection Can Be Prevented by Opening the Blood-Brain Barrier

Roy

Hooper

2007

J Virol

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Silver-haired bat rabies virus (SHBRV) infection induces a strong virus-specific immune response in the periphery of the host, but death is common due to the failure to open the blood-brain barrier (BBB) and deliver immune effectors to central nervous system (CNS) tissues. Mice with an SJL background are less susceptible to lethal infection with rabies viruses. In addition, these animals are known to have reduced hypothalamuspituitary-adrenal (HPA) axis activity and an elevated capacity to mediate CNS inflammatory responses. We show here that approximately one-half of PLSJL mice survive an SHBRV infection that is invariably lethal for 129/SvEv mice. This difference is associated with the elevated capacity of PLSJL mice to mediate BBB permeability changes in response to the infection. The induction of more extensive BBB permeability and CNS inflammation in these animals results in greater virus clearance and improved survival. On the other hand, treatment of SHBRV-infected PLSJL mice with the steroid hormone dehydroepiandrosterone reduced BBB permeability changes and caused greater mortality. We conclude that the infiltration of immune effectors across the BBB is critical to surviving a rabies virus infection and that HPA axis activity may influence this process.Fluid exchange and the entry of circulating cells and macromolecules into central nervous system (CNS) tissues are regulated by the blood-brain barrier (BBB), a specialization of the neurovasculature (11). While the loss of BBB integrity is often associated with pathological changes in the CNS tissues (1, 12, 25), transiently increased BBB permeability can be therapeutic. An example is when immune effectors are delivered to CNS tissues to clear an infection with the attenuated rabies virus (RV) strain CVS-F3 (21). The clearance of this virus from the CNS of 129/SvEv mice occurs without signs of disease and is associated with enhanced BBB permeability which is largely restricted to the cerebellum (21). The absence of this beneficial enhancement of BBB permeability can lead to a CNS infection becoming lethal, as is evidently the case for infection with the highly pathogenic silver-haired bat-associated RV (SHBRV) (23), the virus that is currently responsible for the majority of human deaths from rabies in the United States and Canada (18). Despite the normal development of RV-specific immunity in peripheral lymphoid organs, increased BBB permeability and immune cell invasion do not occur in the CNS tissues of SHBRV-infected 129/SvEv mice (23). Consequently, the virus is not cleared, and the animals die (23).While the antiviral immune response cannot clear SHBRV from the CNS tissues of 129/SvEv mice, immune cells adoptively transferred from these animals are capable of causing elevated BBB permeability as well as CNS inflammation and clearance of CVS-F3 from the CNS of rag2 Ϫ/Ϫ mice (23). We therefore speculated that the BBB in the cerebellum of SHBRV-infected animals becomes refractory to the signals that trigger enhanced permeability, and the virus-clearin...

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“…In addition, the medications against allergic symptoms often contain steroids. Steroid hormones and their metabolic intermediates have a variety of immunological effects [53][54][55][56]. There are several indications that corticosteroids suppress adrenal androgen levels (e.g.…”

Section: Discussionmentioning

confidence: 99%

Menopausal status and factors affecting cessation of menses in the region of Bonn, Germany

et al. 2007

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AbstractBecause of the high prevalence of hormone use and reproductive surgeries in Western women natural menopause is a less frequent condition. Our aim was to examine the influences of hormonal and other factors on timing of cessation of menses. We analysed population controls of a German case-control study on breast cancer risks. The sample comprised N=829 women without hysterectomy or bilateral oophorectomy. We estimated the risk for the occurrence of last menses by Cox proportional hazard modelling. For calculating hazard rate ratios (HRR) and 95% confidence intervals (CI) women with menstrual cycles up to one year before interview were censored at that age. Median age at cessation of menses was 50 years (inter-quartile range 47–53 years). A significant later cessation of menses resulted from oral contraceptive use (HRR 0.74, 95% CI 0.59–0.93 for up to 10 years), and hormone therapy use until last menses (HRR 0.57, 95% CI 0.47–0.70). Also, thyroidal medications were associated with a delayed cessation of menses (HRR 0.64, 95% CI 0.42–0.96 for more than 10 years of use). Smoking until at least two years before last menses and allergies revealed an earlier cessation of bleedings (HRR 1.50, 95% CI 1.22–1.83 and HRR 1.28, 95% CI 1.07–1.53 respectively). Natural menopause is difficult to determine. Factors affecting the ovaries or the endocrine system can modulate timing of menopause. Endocrine biomarkers should be additionally taken into account when defining menopausal status.

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Dehydroepiandrosterone, Dehydroepiandrosterone Sulfate and Related Steroids: Their Role in Inflammatory, Allergic and Immunological Disorders

Cited by 106 publications

References 144 publications

HIV–TB coinfection impairs CD8⁺ T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses

HIV–TB coinfection impairs CD8⁺ T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses

Lethal Silver-Haired Bat Rabies Virus Infection Can Be Prevented by Opening the Blood-Brain Barrier

Menopausal status and factors affecting cessation of menses in the region of Bonn, Germany

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Dehydroepiandrosterone, Dehydroepiandrosterone Sulfate and Related Steroids: Their Role in Inflammatory, Allergic and Immunological Disorders

Cited by 106 publications

References 144 publications

HIV–TB coinfection impairs CD8+ T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses

HIV–TB coinfection impairs CD8+ T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses

Lethal Silver-Haired Bat Rabies Virus Infection Can Be Prevented by Opening the Blood-Brain Barrier

Menopausal status and factors affecting cessation of menses in the region of Bonn, Germany

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HIV–TB coinfection impairs CD8⁺ T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses

HIV–TB coinfection impairs CD8⁺ T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses