Orchiectomy and dehydroepiandrosterone therapy in \'Trypanosoma cruzi\' infected Wistar rats

A tripanossomíase ainda representa importante endemia nas Américas refletindo-se no sentido sócio-econômico onde é responsabilizada pelas taxas de aposentadoria precoce, como conseqüência direta da doença. As terapias até então utilizadas não promovem a cura total da doença além de provocarem efeitos colaterais danosos ao organismo do hospedeiro. É de conhecimento que os esteróides gonadais exercem profunda influência no curso das infecções, e no caso especifico da doença de Chagas, a orquiectomia leva a um estado de maior resistência do hospedeiro a \'Trypanosoma cruzi\'. O DHEA através de suas ações imuno-regulatórias promove o direcionamento da resposta celular do hospedeiro, que por sua vez é efetiva no controle da replicação de distintos patógenos como vírus, bactérias e protozoários. Portanto, a proposta do trabalho é inédita, pois avaliou o sinergismo entre a administração do DHEA e a orquiectomia no direcionamento da resposta imune do hospedeiro no decurso da infecção chagásica experimental em ratos Wistar machos infectados com a cepa y de \'T. cruzi\'. A parasitemia sofreu drástica redução para os grupos orquiectomizados e sujeitos a terapia com DHEA. Da mesma forma os parâmetros imunológicos analisados apresentaram aumento significante das concentrações de IFN-g, IL-12 e NO bem como do número de macrófagos. A histopatologia nos revelou que a orquiectomia e o tratamento com DHEA promoveram melhor reorganização do tecido cardíaco, bem como redução do número e tamanho dos ninhos de amastigotas existentes. Todos esses dados nos levam a crer que a ação sinérgica da terapia associada à orquiectomia promoveu direcionamento da resposta imune do tipo Th1 reduzindo os processos patológicos desencadeados pela infecção chagásica.The ability of the gonadal hormones to influence and induce diverse immunological functions during the course of several parasitic infections has been extensively studied in the latest decades. Dehydroepiandrosterone and its sulphate are the most abundant steroid hormones secreted by the human adrenal cortex and are considered potent immune-activators. In this experiment, it was examined the effects of orchiectomy on the course of Trypanosoma cruzi infection in rats, treated and untreated with DHEA, by comparing blood and cardiac parasitism, macrophages number, Nitric Oxide and IFN-g levels. Orchiectomy led animals to enhanced resistance against infection by elevated number of macrophages, enhanced concentrations of NO and IFN-g and reduced amastigote burdens in heart when compared to control animals. DHEA replacement exerted a synergic effect, up-modulating the immune. Certainly male sex steroids play fundamental role in determining the fate of disease, through the regulation and modulation of the activity of the immune response

The immunomodulatory effects of prolactin during the acute phase of experimental Chagas\' disease

Durante a infecção por Trypanosoma cruzi, o sistema endócrino exerce importante influência no direcionamento da resposta imune do hospedeiro. A prolactina é um dos diversos hormônios envolvidos em uma série de complexas interações com o sistema imunológico, participando diretamente do processo de imunorregulação. As pesquisas relacionadas com a administração de hormônios em modelos experimentais infectados por T. cruzi visam comprovar a modulação dos mecanismos de defesa por estas substâncias e contribuem para a busca de novas terapias auxiliares e melhorias no tratamento convencional da Doença de Chagas. O objetivo deste trabalho foi elucidar o papel da prolactina na modulação do sistema imune durante a fase aguda da doença de Chagas experimental, através da administração desta substância em ratos Wistar jovens infectados com a cepa Y de T.cruzi. O envolvimento e o perfil de ativação das células de defesa durante a infecção aguda foram analisados, utilizando-se ensaios de linfoproliferação, apoptose de linfócitos e análise de marcadores celulares. Além disso, outros parâmetros imunológicos também foram avaliados, entre eles, citocinas intracelulares IFN-?, TNF-?, IL-4 e IL-10, quimiocina MCP-1 e óxido nítrico. Os animais submetidos ao tratamento com prolactina apresentaram redução significativa na parasitemia sanguínea, bem como diminuição na apoptose celular e elevados percentuais de células essenciais na resposta imune do hospedeiro frente ao parasita. Desta forma, os dados obtidos neste trabalho demonstram os efeitos estimulatórios da prolactina e corroboram a ideia da utilização de substâncias imunomoduladoras no desenvolvimento de novas estratégias terapêuticas, que possam promover o equilíbrio da resposta imune do hospedeiro frente à infecção, prevenindo os possíveis danos teciduais observados tanto na fase aguda como crônica da doença de Chagas.During the course of infection by Trypanosoma cruzi, the host immune system is involved in distinct, complex interactions with the endocrine system, and prolactin (PRL) is one of several hormones involved in immunoregulation. Numerous studies have demonstrated that the modulation of the immune system with the administration of regulatory hormones in different experimental models infected with T. cruzi, are very important inciting the investigation of new therapies for Chagas\' disease. The role of PRL as a possible factor in the modulation of the immune response was the target of this study using as animal model young rats infected with the Y strain of T. cruzi, in the attempt to demonstrate the relationship between the neuroendocrine system and the immune response involved in the acute phase of the experimental Chagas\' disease. For this purpose, some immune parameters were analyzed: dosages of cytokines IFN-?, TNF-?, IL-4, IL-10 and chemokine MCP-1, phenotypic analysis of cell subsets by flow cytometry, production of nitric oxide, lymphoproliferation and apoptosis of splenocytes. Therapy with PRL caused a significant decrease in parasitemia during the acute phase. PRL also triggered an increase in the percentage of cells of the innate and adaptive immune response and decreased apoptosis. Thus, the data obtained in this study corroborate the idea of using substances such as PRL in the development of new therapeutic strategies that can modulate the inflammatory response, contributing to the balance of the host body against infection, preventing the possible tissue damage observed in both acute and chronic Chagas\' disease

Orchiectomy and dehydroepiandrosterone therapy in \'Trypanosoma cruzi\' infected Wistar rats

A tripanossomíase ainda representa importante endemia nas Américas refletindo-se no sentido sócio-econômico onde é responsabilizada pelas taxas de aposentadoria precoce, como conseqüência direta da doença. As terapias até então utilizadas não promovem a cura total da doença além de provocarem efeitos colaterais danosos ao organismo do hospedeiro. É de conhecimento que os esteróides gonadais exercem profunda influência no curso das infecções, e no caso especifico da doença de Chagas, a orquiectomia leva a um estado de maior resistência do hospedeiro a \'Trypanosoma cruzi\'. O DHEA através de suas ações imuno-regulatórias promove o direcionamento da resposta celular do hospedeiro, que por sua vez é efetiva no controle da replicação de distintos patógenos como vírus, bactérias e protozoários. Portanto, a proposta do trabalho é inédita, pois avaliou o sinergismo entre a administração do DHEA e a orquiectomia no direcionamento da resposta imune do hospedeiro no decurso da infecção chagásica experimental em ratos Wistar machos infectados com a cepa y de \'T. cruzi\'. A parasitemia sofreu drástica redução para os grupos orquiectomizados e sujeitos a terapia com DHEA. Da mesma forma os parâmetros imunológicos analisados apresentaram aumento significante das concentrações de IFN-g, IL-12 e NO bem como do número de macrófagos. A histopatologia nos revelou que a orquiectomia e o tratamento com DHEA promoveram melhor reorganização do tecido cardíaco, bem como redução do número e tamanho dos ninhos de amastigotas existentes. Todos esses dados nos levam a crer que a ação sinérgica da terapia associada à orquiectomia promoveu direcionamento da resposta imune do tipo Th1 reduzindo os processos patológicos desencadeados pela infecção chagásica.The ability of the gonadal hormones to influence and induce diverse immunological functions during the course of several parasitic infections has been extensively studied in the latest decades. Dehydroepiandrosterone and its sulphate are the most abundant steroid hormones secreted by the human adrenal cortex and are considered potent immune-activators. In this experiment, it was examined the effects of orchiectomy on the course of Trypanosoma cruzi infection in rats, treated and untreated with DHEA, by comparing blood and cardiac parasitism, macrophages number, Nitric Oxide and IFN-g levels. Orchiectomy led animals to enhanced resistance against infection by elevated number of macrophages, enhanced concentrations of NO and IFN-g and reduced amastigote burdens in heart when compared to control animals. DHEA replacement exerted a synergic effect, up-modulating the immune. Certainly male sex steroids play fundamental role in determining the fate of disease, through the regulation and modulation of the activity of the immune response

Trypanosoma cruzi: The effects of zinc supplementation during experimental infection

it is well recognized that zinc is an essential trace element, influencing growth and affecting the development and integrity of the immune system. The use of oligoelements as zinc can be considered a tool in modulating the effectiveness of the immune response. In this work zinc was daily and orally supplied in male Wistar rats infected with the Y strain of Trypanosoma cruzi. Parasiternia was evaluated and a significant reduction on blood parasites was observed. In order to check some immunological parameters peritoneal macrophages were counted revealing higher percentages for zinc supplied group. Consequently enhanced concentrations of IFN-gamma was found and for the first time NO was evaluated in T cruzi infected animals under the influence of zinc therapy, revealing enhanced concentrations when compared to. unsupplied counterparts. We conclude that zinc is able to up-regulate the host`s immune response against parasite replication. (c) 2007 Elsevier Inc. All rights reserved

Zinc supplementation increases resistance to experimental infection by Trypanosoma cruzi

It is well recognized that zinc is an essential trace element for all organisms, influencing growth and affecting the development and integrity of the immune system. It is also well known that the protective response against Trypanosoma cruzi depends on both innate and acquired immunity and for the control of the parasite load and host survival, the participation of special cells such natural killer (NK), T and B lymphocytes and macrophages are required. So the aims of this study were to evaluate the effects of zinc supplementation on the host`s immune response infected with T cruzi. Our data point in the direction that zinc supplementation triggered enhanced thymocyte and splenocyte proliferation as compared to unsupplied group of animals. It is also important to emphasize that interleukin-12 (IL-12) participates in the resistance to several intracellular pathogens including T cruzi. Our findings demonstrate an enhanced production of IL-12 during the acute phase of infection in zinc-supplied groups. So we conclude that zinc supplementation leads to an effective host`s immune response by up-modulating the host`s immune response, thus contributing in the reduction of blood parasites and the harmful pathogenic effects of the experimental Chagas` disease. (c) 2008 Elsevier B.V. All rights reserved

Immunomodulatory effects of zinc and DHEA on the Th-1 immune response in rats infected with Trypanosoma cruzi

Chagas` disease is considered the sixth most important neglected tropical disease worldwide. Considerable knowledge has been accumulated concerning the role of zinc on cellular immunity. The steroid hormone dehydroepiandrosterone (DHEA) is also known to modulate the immune system. The aims of this paper were to investigate a possible synchronization of their effects on cytokines and NO production and the resistance to Trypanosoma cruzi during the acute phase of infection. It was found that zinc, DHEA or zinc and DHEA supplementation enhanced the immune response, as evidenced by a significant reduction in parasitemia levels. Zinc and DHEA supplementation exerted additive effects on the immune response by elevation of macrophage counts, and by increasing concentrations of IFN-gamma and NO. (C) 2009 Elsevier GmbH. All rights reserved.CAPE

Trypanosoma cruzi: The effects of zinc supplementation in the immune response during the course of experimental disease

Zinc is an essential nutritional component required for normal development and maintenance of immune functions. The possible effects of zinc in upregulating the host immune response during the acute and chronic phases of experimental Chagas` disease were evaluated. In young, infected and Zn-supplemented animals, higher concentrations of IFN-gamma and NO were observed. During the chronic phase, decreased concentrations of NO and IFN-gamma were found for older infected animals that received Zn supplementation. For young animals, hearts from Zn-supplemented groups displayed reduced inflammatory infiltrate, heart weight and number of amastigote burdens. For older, infected and Zn-supplemented animals amastigote nests were absent with reduced inflammatory cell infiltrate. This study identifies a potentially novel therapeutic approach that could control the parasite load during acute phase of disease, consequently preventing the deleterious, parasite-elicited responses observed during chronic phase. (C) 2008 Elsevier Inc. All rights reserved.CAPE

Dehydroepiandrosterone increases resistance to experimental infection by Trypanosoma cruzi

Dehydroepiandrosterone (DHEA) enhances immune responses against a wide range of viral, bacterial, and parasitic pathogens. In a previous study, we reported that administration of DHEA significantly decreased the numbers of blood parasites in Trypanosoma cruzi experimental infection. The present study was undertaken to determine the effectiveness of DHEA in reducing the severity of acute phase T cruzi infection of male and female Wistar rats. Animals were treated subcutaneously with 40 mg/kg body weight/day of DHEA. The concentration of nitric oxide (NO) was determined in spleen peritoneal cavity. Interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) were determined in the sera of uninfected and infected animals. DHEA treatment augments NO production for both sexes after in vitro LPS treatment for uninfected animals. Infection triggered enhanced NO levels although not significant. IL-2 and IFN-gamma were detectable in higher concentrations in treated and infected rats of both genders when compared to untreated controls. These data suggest that DHEA may have a potent immunoregulatory function that can affect the course of T cruzi infection. (c) 2008 Elsevier B.V. All rights reserved

DHEA and testosterone therapies in Trypanosoma cruzi-infected rats are associated with thymic changes

The ability of the gonadal hormones to influence diverse immunological functions during the course of several infections has been extensively studied in the latest decades. Testosterone has a suppressive effect on immune response of vertebrates and increases susceptibility toward numerous parasitic diseases. Dehydroepiandrosterone is an abundant steroid hormone secreted by the human adrenal cortex and it is considered potent immune-activator. In this paper, it was examined the effects of DHEA and testosterone supplementation in the thymic atrophy in rats infected with Trypanosoma cruzi, by comparing blood parasitism, thymocyte proliferation, TNF-alpha and IL-12 levels. Our data point in the direction that DHEA treatment triggered enhanced thymocyte proliferation as compared to its infected counterparts and reduced production of TNF-alpha during the acute phase of infection. Oppositely, the lowest values for cells proliferation and IL-12 concentrations were reached in testosterone-supplied animals. The combined treatment testosterone and DHEA improves the effectiveness of the host`s immune response, reducing blood parasites and the immunosuppressive effects of male androgens besides increasing IL-12 concentrations and decreasing TNF-alpha levels. (C) 2010 Elsevier Ltd. All rights reserved.CAPE

Trypanosoma cruzi: Orchiectomy and dehydroepiandrosterone therapy in infected rats

The ability of gonadal hormones to influence and induce diverse immunological functions during the course of a number of parasitic infections has been extensively studied in the latest decades. Dehydroepiandrosterone and its sulfate are the most abundant steroid hormones secreted by the human adrenal cortex and are considered potent immune-activators. The effects of orchiectomy on the course of Trypanosoma cruzi infection in rats, treated and untreated with DHEA were examined, by comparing blood and cardiac parasitism, macrophage numbers, nitric oxide and IFN-gamma levels. Orchiectomy enhanced resistance against infection with elevated numbers of macrophages, enhanced concentrations of NO and IFN-gamma and reduced amastigote burdens in heart when compared to control animals. DHEA replacement exerted a synergistic effect, up-modulating the immune response. Male sex steroids appear to play fundamental role in determining the outcome of disease, through the regulation and modulation of the activity of the immune response. (C) 2008 Elsevier Inc. All rights reserved.CAPE