Safety and Activity of the Immune Modulator HE2000 on the Incidence of Tuberculosis and Other Opportunistic Infections in AIDS Patients

Stickney, Dwight R.; Noveljic, Zoja; Garsd, Armando; Destiche, Daniel A.; Frincke, James M.

doi:10.1128/aac.01446-06

Cited by 25 publications

(20 citation statements)

References 15 publications

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Section: Discussionsupporting

confidence: 91%

“…The latter theory could be in fact involved as EpiBr has anti-inflammatory properties and it is also able to induce cellular immunity that may aid the control of infections [19, 41, 42]. Our results in vivo are also in agreement with previous studies supporting a potential pharmacological use of EpiBr to treat infections such as tuberculosis, AIDS, and malaria [19, 21, 41, 42]. Thus, administration of intramuscular HE2000 in patients with P. falciparum malaria resulted in a 50% reduction of parasitemia with notably improve in symptomatology and mild adverse events [43].…”

Section: Discussionmentioning

confidence: 99%

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A New Parasiticidal Compound inT. soliumCysticercosis

Hernández-Bello

Escobedo

Carrero

et al. 2013

BioMed Research International

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The effect of 16α-bromoepiandrosterone (EpiBr), a dehydroepiandrosterone (DHEA) analogue, was tested on the cysticerci of Taenia solium, both in vitro and in vivo. In vitro treatment of T. solium cultures with EpiBr reduced scolex evagination, growth, motility, and viability in dose- and time-dependent fashions. Administration of EpiBr prior to infection with T. solium cysticerci in hamsters reduced the number and size of developed taenias in the intestine, compared with controls. These effects were associated to an increase in splenocyte proliferation in infected hamsters. These results leave open the possibility of assessing the potential of this hormonal analogue as a possible antiparasite drug, particularly in cysticercosis and taeniosis.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

A New Parasiticidal Compound inT. soliumCysticercosis

Hernández-Bello

Escobedo

Carrero

et al. 2013

BioMed Research International

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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]. We have previously demonstrated that in vitro treatment of PBMCs from HIV-TB patients with DHEA increased Mtb-specific IFN-γ responses and decreased FoxP3 expression in regulatory T cells, thus inducing a bias toward a protective antitubercular immune response [19].…”

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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“…Acquired immunodefi ciency syndrome (AIDS) is defi ned as the occurrence of life-threatening opportunistic infections (OIs), malignancies, neurological diseases and other specifi c illnesses in patients with human immunodefi ciency virus (HIV) infection and CD4 counts <200 cells/mm 3 .…”

Section: Introductionmentioning

confidence: 99%

“…[2] OIs are a chief cause of AIDS related mortality [3] and timely intervention helps to increase longevity and to prevent transmission of these infections in the community. [2] The National AIDS Control Organization (NACO), India classifi es OIs into 12 categories and has provided guidelines for their prevention and treatment.…”

Section: Introductionmentioning

confidence: 99%

A study of utilization pattern, efficacy and safety of drugs prescribed for opportunistic infections in Human Immunodeficiency Virus infected patients

Kapadia

Desai

Dikshit

et al. 2014

Int J Med Public Health

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Safety and Activity of the Immune Modulator HE2000 on the Incidence of Tuberculosis and Other Opportunistic Infections in AIDS Patients

Cited by 25 publications

References 15 publications

A New Parasiticidal Compound inT. soliumCysticercosis

A New Parasiticidal Compound inT. soliumCysticercosis

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

A study of utilization pattern, efficacy and safety of drugs prescribed for opportunistic infections in Human Immunodeficiency Virus infected patients

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Safety and Activity of the Immune Modulator HE2000 on the Incidence of Tuberculosis and Other Opportunistic Infections in AIDS Patients

Cited by 25 publications

References 15 publications

A New Parasiticidal Compound inT. soliumCysticercosis

A New Parasiticidal Compound inT. soliumCysticercosis

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

A study of utilization pattern, efficacy and safety of drugs prescribed for opportunistic infections in Human Immunodeficiency Virus infected patients

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