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1.
Int J Mol Sci ; 22(21)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34768903

RESUMO

The hypothalamus-pituitary-adrenal (HPA) axis was described as the principal component of the stress response 85 years ago, along with the acute-phase reaction, and the defense response at the tissue level. The orchestration of these processes is essential since systemic inflammation is a double-edged sword; whereas inflammation that is timely and of appropriate magnitude is beneficial, exuberant systemic inflammation incites tissue damage with potentially devastating consequences. Apart from its beneficial cardiovascular and metabolic effects, cortisol exerts a significant immunoregulatory role, a major attribute being that it restrains the excessive inflammatory reaction, thereby preventing unwanted tissue damage. In this review, we will discuss the role of the HPA axis in the normal stress response and in critical illness, especially in critically ill patients with coronavirus disease 2019 (COVID-19). Finally, a chapter will be dedicated to the findings from clinical studies in critical illness and COVID-19 on the expression of the mediator of glucocorticoid actions, the glucocorticoid receptor (GCR).


Assuntos
COVID-19/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/virologia , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/virologia , Receptores de Glucocorticoides/metabolismo , Estado Terminal , Glucocorticoides/metabolismo , Humanos , Estresse Fisiológico
2.
Reprod Sci ; 28(10): 2735-2742, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33415647

RESUMO

Coronavirus disease 2019 (COVID-19), which resulted from the pandemic outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes a massive inflammatory cytokine storm leading to multi-organ damage including that of the brain and testes. While the lungs, heart, and brain are identified as the main targets of SARS-CoV-2-mediated pathogenesis, reports on its testicular infections have been a subject of debate. The brain and testes are physiologically synchronized by the action of gonadotropins and sex steroid hormones. Though the evidence for the presence of the viral particles in the testicular biopsies and semen samples from COVID-19 patients are highly limited, the occurrence of testicular pathology due to abrupt inflammatory responses and hyperthermia has incresingly been evident. The reduced level of testosterone production in COVID-19 is associated with altered secretion of gonadotropins. Moreover, hypothalamic pathology which results from SARS-CoV-2 infection of the brain is also evident in COVID-19 cases. This article revisits and supports the key reports on testicular abnormalities and pathological signatures in the hypothalamus of COVID-19 patients and emphasizes that testicular pathology resulting from inflammation and oxidative stress might lead to infertility in a significant portion of COVID-19 survivors. Further investigations are required to monitor the reproductive health parameters and HPG axis abnormalities related to secondary pathological complications in COVID-19 patients and survivors.


Assuntos
COVID-19/epidemiologia , Fertilidade , Hipotálamo/patologia , Infertilidade Masculina/epidemiologia , SARS-CoV-2/patogenicidade , Testículo/patologia , Animais , Atrofia , COVID-19/diagnóstico , COVID-19/virologia , Gonadotropinas/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/patologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipotálamo-Hipofisário/virologia , Hipotálamo/metabolismo , Hipotálamo/fisiopatologia , Hipotálamo/virologia , Incidência , Infertilidade Masculina/patologia , Infertilidade Masculina/fisiopatologia , Infertilidade Masculina/virologia , Masculino , Testículo/metabolismo , Testículo/fisiopatologia , Testículo/virologia , Testosterona/metabolismo
3.
ACS Chem Neurosci ; 11(13): 1868-1870, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32605374

RESUMO

Cytokine storm in COVID-19 is characterized by an excessive inflammatory response to SARS-CoV-2 that is caused by a dysregulated immune system of the host. We are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of nucleus tractus solitarius (NTS) may be responsible for the cytokine storm in COVID 19. The inflamed NTS may result in a dysregulated cholinergic anti-inflammatory pathway and hypothalamic-pituitary-adrenal axis.


Assuntos
Betacoronavirus/metabolismo , Infecções por Coronavirus/metabolismo , Citocinas/metabolismo , Pneumonia Viral/metabolismo , Núcleo Solitário/metabolismo , Axônios/imunologia , Axônios/metabolismo , Axônios/virologia , Betacoronavirus/imunologia , COVID-19 , Infecções por Coronavirus/imunologia , Nervos Cranianos/imunologia , Nervos Cranianos/metabolismo , Nervos Cranianos/virologia , Citocinas/imunologia , Humanos , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/virologia , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Pandemias , Sistema Hipófise-Suprarrenal/imunologia , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/virologia , Pneumonia Viral/imunologia , SARS-CoV-2 , Núcleo Solitário/imunologia , Núcleo Solitário/virologia
4.
Endocrine ; 68(2): 251-252, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32346813
5.
J Acquir Immune Defic Syndr ; 75(3): e65-e70, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28141781

RESUMO

OBJECTIVE: Glucocorticoids are released in response to stress and alter cognition and brain function through both rapid nongenomic and slow genomic mechanisms. Administration of glucocorticoids in the form of hydrocortisone enhances aspects of learning and memory in individuals with PTSD but impairs these abilities in healthy individuals. We examine the time-dependent effects of glucocorticoids on cognition in HIV-infected men. METHODS: In a double-blind placebo-controlled crossover study, we examined the time-dependent effects of a single low dose of hydrocortisone [10 mg; low-dose hydrocortisone (LDH)] on cognition in 45 HIV-infected men. Participants were randomized to receive either LDH or placebo and one month later, were given the opposite treatment. At each intervention session, cognition was assessed 30 minutes (assessing nongenomic effects) and 4 hours (assessing genomic effects) after pill administration. Self-reported stress/anxiety and cortisol/cytokines in saliva were measured throughout each session. RESULTS: Compared with placebo, LDH doubled salivary cortisol levels. Cortisol returned to baseline 4 hours postadministration. At the 30-minute assessment, LDH enhanced verbal learning compared with placebo. Greater increases in cortisol were associated with greater enhancements in verbal learning. LDH did not affect subjective stress/anxiety or any other cognitive outcomes at the 30-minute or 4-hour time point. CONCLUSIONS: The rapid effects of LDH on verbal learning suggests a nongenomic mechanism by which glucocorticoids can enhance cognition in HIV-infected men. The nonenduring nature of this enhancement may limit its clinical utility but provides insight into mechanisms underlying the effects of acute glucocorticoids on learning.


Assuntos
Anti-Inflamatórios/uso terapêutico , Transtornos Cognitivos/complicações , Transtornos Cognitivos/tratamento farmacológico , Infecções por HIV/complicações , Hidrocortisona/uso terapêutico , Aprendizagem Verbal/efeitos dos fármacos , Adolescente , Adulto , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/virologia , Estudos Cross-Over , Método Duplo-Cego , Infecções por HIV/fisiopatologia , Infecções por HIV/psicologia , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipotálamo-Hipofisário/virologia , Masculino , Memória de Curto Prazo/efeitos dos fármacos , Pessoa de Meia-Idade , Testes Neuropsicológicos , Receptores de Glucocorticoides/efeitos dos fármacos , Saliva/metabolismo , Resultado do Tratamento , Adulto Jovem
6.
PLoS One ; 9(4): e87180, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24763072

RESUMO

Central nervous system (CNS) metabolic profiles were examined from rabies virus (RABV)-infected mice that were either mock-treated or received post-exposure treatment (PET) with a single dose of the live recombinant RABV vaccine TriGAS. CNS tissue harvested from mock-treated mice at middle and late stage infection revealed numerous changes in energy metabolites, neurotransmitters and stress hormones that correlated with replication levels of viral RNA. Although the large majority of these metabolic changes were completely absent in the brains of TriGAS-treated mice most likely due to the strong reduction in virus spread, TriGAS treatment resulted in the up-regulation of the expression of carnitine and several acylcarnitines, suggesting that these compounds are neuroprotective. The most striking change seen in mock-treated RABV-infected mice was a dramatic increase in brain and serum corticosterone levels, with the later becoming elevated before clinical signs or loss of body weight occurred. We speculate that the rise in corticosterone is part of a strategy of RABV to block the induction of immune responses that would otherwise interfere with its spread. In support of this concept, we show that pharmacological intervention to inhibit corticosterone biosynthesis, in the absence of vaccine treatment, significantly reduces the pathogenicity of RABV. Our results suggest that widespread metabolic changes, including hypothalamic-pituitary-adrenal axis activation, contribute to the pathogenesis of RABV and that preventing these alterations early in infection with PET or pharmacological blockade helps protect brain homeostasis, thereby reducing disease mortality.


Assuntos
Encéfalo/metabolismo , Vírus da Raiva/imunologia , Raiva/metabolismo , Ácido 3-Hidroxibutírico/metabolismo , Imunidade Adaptativa , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Encéfalo/virologia , Carnitina/análogos & derivados , Carnitina/metabolismo , Corticosterona/sangue , Progressão da Doença , Metabolismo Energético , Feminino , Expressão Gênica , Interações Hospedeiro-Patógeno , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/virologia , Camundongos , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/virologia , Piridinas/farmacologia , Piridinas/uso terapêutico , Raiva/tratamento farmacológico , Raiva/imunologia , Carga Viral , Proteínas Virais/genética , Proteínas Virais/metabolismo , Vacinas Virais/uso terapêutico
7.
PLoS One ; 7(12): e51029, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23251416

RESUMO

Except severe pulmonary disease caused by influenza virus infection, an impaired immune system is also a clinic characteristic. However, the mechanism(s) of influenza virus infection-induced depletion of B cells was unknown. Here, we compared the effect of two variant virulence H9N2 virus infections on mouse B cells. Our study found that the infection with highly pathogenic virus (V) of led to depletion of spleen B cells and bone marrow (BM) early B cells, compared to lowly pathogenic virus (Ts). Moreover, high apoptosis and cell cycle arrest in spleen and BM were detected, suggesting important factors for the reduction of B cells in both organs. Further, this effect was not caused by virus replication in spleen and BM. Compared to Ts virus infection, V virus resulted in higher glucocorticoids (GCs) and lower leptin level in plasma. Intraperitoneal GCs receptor antagonist RU486 injection was sufficient to prevent the loss of spleen B cell and BM pro- and immature B cells, but similar result was not observed in leptin-treated mice. Depletion of spleen B cells and BM pro-B cells was also reversed by chemical sympathectomy mediated by the norepinephrine (NE) analog 6-hydroxydopamine (6-OHDA), but the treatment didn't affect the GCs level. This study demonstrated that depletion of B cells induced by H9N2 AIV was dependent on HPA axis and sympathetic response.


Assuntos
Linfócitos B/imunologia , Sistema Hipotálamo-Hipofisário/imunologia , Vírus da Influenza A Subtipo H9N2/imunologia , Influenza Aviária/imunologia , Sistema Hipófise-Suprarrenal/imunologia , Sistema Nervoso Simpático/imunologia , Animais , Apoptose/imunologia , Linfócitos B/patologia , Linfócitos B/virologia , Galinhas , Feminino , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/patologia , Sistema Hipotálamo-Hipofisário/virologia , Sistema Imunitário/patologia , Sistema Imunitário/virologia , Influenza Aviária/sangue , Influenza Aviária/patologia , Leptina/sangue , Camundongos , Sistema Hipófise-Suprarrenal/patologia , Sistema Hipófise-Suprarrenal/virologia , Sistema Nervoso Simpático/patologia , Sistema Nervoso Simpático/virologia
8.
Hormones (Athens) ; 7(3): 205-16, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18694859

RESUMO

Abnormalities of the hypothalamic-pituitary-adrenal (HPA) axis have been documented in HIV patients in the early as well as late stages of the infection and range from subtle subclinical disturbances to frank adrenal insufficiency. Potential etiologies of these disorders include opportunistic infections, neoplasms, drugs administered to treat infections, cytokine abnormalities associated with the HIV disease process and acquired alterations in tissue sensitivity to glucocorticoids. In this article, we present a concise review of HPA abnormalities in HIV infection and disease with regard to their etiology with emphasis on syndromes of hypersensitivity/resistance to glucocorticoids associated with antiviral medications and/or the HIV infection itself.


Assuntos
Doenças das Glândulas Suprarrenais/etiologia , Infecções por HIV/complicações , HIV-1/patogenicidade , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Corticosteroides/uso terapêutico , Doenças das Glândulas Suprarrenais/fisiopatologia , Doenças das Glândulas Suprarrenais/terapia , Insuficiência Adrenal/etiologia , Insuficiência Adrenal/fisiopatologia , Fármacos Anti-HIV/efeitos adversos , Síndrome de Cushing/etiologia , Síndrome de Cushing/fisiopatologia , Resistência a Medicamentos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , Síndrome de Lipodistrofia Associada ao HIV/fisiopatologia , Síndrome de Lipodistrofia Associada ao HIV/virologia , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/virologia , Resistência à Insulina , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/virologia
9.
Psychoneuroendocrinology ; 33(1): 30-40, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17993249

RESUMO

Human immunodeficiency virus type 1 (HIV-1) infection causes a wide spectrum of abnormalities in neurological, neuropsychological, and neuroendocrinological functions. Several studies report disturbance in autonomic nervous system (ANS) and hypothalamic pituitary-adrenal (HPA) axis function in HIV-1B infected individuals. However, no such investigations on the effect of HIV-1 clade C infection, particularly during the initial phase of the disease progression, have been reported. The present investigations were carried out longitudinally over a 2-year period at 12 monthly intervals in clinically asymptomatic HIV-1 clade C seropositive patients (n=120) and seronegative control subjects (n=29). We determined both the basal levels and the dynamic changes in plasma levels of norepinephrine (NE), epinephrine (E), adrenocorticotrophic hormone (ACTH) and cortisol (CORT). Studies were also extended longitudinally (at three separate yearly visits of each participant), to evaluate the response of autonomic and HPA axis to mirror star tracing challenge test (MSTCT) and the values were determined as area under the curve (AUC, corrected for baseline levels of NE, E, ACTH, and CORT). The findings show that the values of basal plasma NE levels, as well as NE response to MSTCT (AUC) at the first visit of HIV-1 seropositive individuals did not differ from those found in the control subjects (NE, pg/ml, HIV-1C=313.5+/-12.7 vs. controls=353.0+/-21.3; p=NS; AUC, HIV-1C=225+/-14.75 vs. controls=232.7+/-19.34; p=NS, respectively). At the subsequent two visits of HIV-1 positive patients however, NE response to MSTCT challenge was progressively attenuated (AUC=235+/-19.5 and 162.7+/-13.6; p<0.01 and 0.05, respectively) compared to that found at the first visit. On the other hand, plasma levels of E as well as E response to MSTCT at the first visit were significantly lower in HIV-1C seropositive individuals compared to those in the control subjects (pg/ml, HIV-1C=77.30+/-5.7 vs. controls=119.1+10.5; p<0.05; AUC, HIV-1C =83.29+/-7.5 vs. controls=172.3+/-18.9; p<0.001), but no further change was observed in AUC of E in response to MSTCT at the two subsequent yearly visits. The basal plasma levels of ACTH in HIV-1C seropositives were not different than in the control subjects (pg/ml: HIV-1C=20.0+/-0.9 vs. controls=23.1+/-1.6; p=NS), but ACTH response to MSTCT in HIV-1C seropositive patients at the first visit was lower than in the controls (AUC, HIV-1C=23.57+/-1.5 vs. controls=30.94+/-3.5; p<0.05), and fluctuated between high and low at the second and third visits (AUC, 28.89+/-2.3 and 21.69+/-2.36, respectively). However, the baseline plasma levels of cortisol as well as the response of cortisol to MSTCT (AUC) in HIV-1C seropositive individuals were higher than in the control subjects at the first visit (mug/dl, HIV-1C=9.83+/-0.39 vs. controls=6.3+/-0.56; p<0.05; AUC, HIV-1C=12.31+/-0.7 vs. control=9.18+/-0.9; p<0.05), and remained high at the two subsequent yearly follow up visits of HIV-1C (AUC, 11.8+/-0.86 and 11.98+/-0.77, respectively). These findings demonstrate attenuated autonomic functions, a disconnection between response of ACTH and cortisol to the MSTCT challenge, and an inverse relationship between plasma levels of catecholamine(s) and cortisol. Since plasma catecholamines and cortisol are the peripheral mediators of the autonomic and HPA axis function, the findings of this study reflect the overall adverse effect of HIV-1C infection on autonomic as well as HPA axis functions. The findings, apart from being the first to demonstrate the progressive dysregulation of autonomic nervous system and HPA axis function among HIV-1C infected seropositive individuals much ahead of the onset of acquired immunodeficiency syndrome (AIDS), also suggest that MSTCT, involving visuoconstructive cognitive abilities, is an effective stressor for unraveling the underlying dysfunctions in the neuroendocrine functions in health and disease.


Assuntos
Soropositividade para HIV/complicações , HIV-1/imunologia , Hidrocortisona/sangue , Destreza Motora/fisiologia , Estresse Psicológico/sangue , Adaptação Fisiológica , Adolescente , Hormônio Adrenocorticotrópico/sangue , Adulto , Análise de Variância , Área Sob a Curva , Sistema Nervoso Autônomo/fisiopatologia , Sistema Nervoso Autônomo/virologia , Estudos de Casos e Controles , Epinefrina/sangue , Feminino , Soronegatividade para HIV , Soropositividade para HIV/sangue , Soropositividade para HIV/psicologia , HIV-1/classificação , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipotálamo-Hipofisário/virologia , Índia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Sistemas Neurossecretores , Norepinefrina/sangue , Sistema Hipófise-Suprarrenal/fisiopatologia , Sistema Hipófise-Suprarrenal/virologia , Valores de Referência , Estatísticas não Paramétricas , Estresse Psicológico/virologia
10.
Przegl Epidemiol ; 60(4): 707-14, 2006.
Artigo em Polonês | MEDLINE | ID: mdl-17682752

RESUMO

Thyroid disorders and diabetes mellitus t. II are the most common disorders observed among of endocrine extrahepatic manifestations of HCV infection. The mechanism of this disorders is still unclear. Two main hypothesis are considered: primary cytopathic effect of virus and secondary-induced autoimmunity. The ability of HCV to infect central nervous system cells seems to be significant in the hypothalamus--epiphysis--axis dysfunction. Further clinical researches are awaited in order to explain phenomenon mentioned above.


Assuntos
Doenças Autoimunes/virologia , Diabetes Mellitus Tipo 2/virologia , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Doenças da Glândula Tireoide/virologia , Sistema Nervoso Central/virologia , Humanos , Sistema Hipotálamo-Hipofisário/virologia
11.
Arch Intern Med ; 162(10): 1095-8, 2002 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-12020177

RESUMO

Although clinical manifestations of adrenal dysfunction are uncommon in patients infected with human immunodeficiency virus (HIV), subclinical functional abnormalities of the hypothalamic-pituitary-adrenal axis are frequent. Patients infected with HIV usually have higher basal serum cortisol and lower serum dehydroepiandrosterone concentrations than HIV-seronegative individuals. This imbalance has been related to progression of the infection by inducing a shift from T(H)1 to T(H)2 immunologic responses. Although, adrenal reserve may be marginal in HIV-infected patients, clinically evident adrenal insufficiency is uncommon and, when present, it is observed in advanced stages of the infection. Hypocortisolemia should be treated regardless of the existence of associated symptoms. On the contrary, hypercortisolemia in the absence of features of Cushing syndrome is common and should not promote treatment nor specific studies. The possible influence that alterations of the adrenal function could have on the patients' immune status and the eventual effect of antiretrovirals on these alterations merit further investigation.


Assuntos
Insuficiência Adrenal/virologia , Hiperfunção Adrenocortical/virologia , Infecções por HIV/complicações , Insuficiência Adrenal/fisiopatologia , Hiperfunção Adrenocortical/fisiopatologia , Fármacos Anti-HIV/farmacologia , Infecções por HIV/tratamento farmacológico , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/virologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/virologia
12.
Neuroendocrinology ; 74(3): 160-6, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11528217

RESUMO

UNLABELLED: Herpes simplex virus type 1 (HSV-1) is a common cause of viral encephalitis, manifested by neuroendocrine and behavioral changes. We have previously demonstrated that HSV-1 induces marked hypothalamo-pituitary-adrenocortical (HPA) axis activation. In this study we characterized the acute effects of HSV-1 on the HPA axis occurring before viral replication and appearance of clinical signs of encephalitis. Since in previous studies we used crude virus preparations which may contain immune factors produced by the infected cells, we tested here the effects of purified HSV-1 virions. HSV-1 was propagated on Vero cells and virions were purified by centrifugation in sucrose gradients. Inactivation of viral infectivity was achieved by UV-irradiation, which caused a million-fold decrease in virus titer, as determined by plaque assay. Intracerebroventricular (ICV) inoculation of crude or purified virions induced a dose dependent increase in serum corticosterone and corticotropin (ACTH). This effect was maximal within 3.5 h postinfection and lasted for 72 h. ICV inoculation of UV-inactivated purified virions caused a marked increase in serum corticosterone and ACTH at 3.5 h, but in contrast to the effect of the active virus, the hormone levels gradually decreased at 24 h, and returned to basal levels at 72 h postinfection. HSV-1-induced HPA axis activation at 3.5 h was completely abolished by pretreatment with interleukin-1 receptor antagonist, injected ICV. Adrenalectomized rats failed to respond to ICV inoculation of purified HSV-1 by increase in ACTH. In contrast, these rats responded to ICV injection of LPS. IN CONCLUSION: (1) HSV-1 can acutely activate the HPA axis before and independently of any viral replication; (2) HSV-1-induced HPA axis activation depends on a permissive action of circulating glucocorticoids and on host derived brain interleukin-1.


Assuntos
Herpesvirus Humano 1/fisiologia , Sistema Hipotálamo-Hipofisário/virologia , Sistema Hipófise-Suprarrenal/virologia , Adrenalectomia , Hormônio Adrenocorticotrópico/sangue , Animais , Centrifugação com Gradiente de Concentração , Corticosterona/sangue , Relação Dose-Resposta a Droga , Herpesvirus Humano 1/efeitos da radiação , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/fisiologia , Injeções Intraventriculares , Proteína Antagonista do Receptor de Interleucina 1 , Lipopolissacarídeos/farmacologia , Masculino , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/fisiologia , Ratos , Ratos Endogâmicos , Sialoglicoproteínas/farmacologia , Fatores de Tempo , Raios Ultravioleta , Vírion/fisiologia , Vírion/efeitos da radiação
14.
J Neuroimmunol ; 98(2): 121-9, 1999 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-10430045

RESUMO

The goal of these studies was to analyze the ability of androstenediol (AED) to counter-regulate the influences of stress on anti-viral immune responses. Male C57BL/6 mice, treated with 320 mg/kg AED were infected with influenza virus and subjected to repeated cycles of restraint (RST). AED blocked RST-mediated suppression of cell recruitment to the draining lymph node, lung NK cell activity, and CD4 + T cell activation. In addition, mice treated with AED had lower pre-corticosterone levels as compared to vehicle controls and the RST-mediated elevation of corticosterone was significantly blunted by AED treatment. These data suggest that AED functions to augment anti-viral immune responses by counter-regulating glucocorticoid function.


Assuntos
Anabolizantes/farmacologia , Androstenodiol/farmacologia , Vírus da Influenza A/imunologia , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/imunologia , Infecções por Orthomyxoviridae/imunologia , Animais , Corticosterona/sangue , Testes Imunológicos de Citotoxicidade , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipotálamo-Hipofisário/virologia , Tolerância Imunológica , Interferon gama/imunologia , Interferon gama/metabolismo , Interleucina-10/imunologia , Interleucina-10/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/virologia , Cinética , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Doenças Linfáticas/imunologia , Doenças Linfáticas/virologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sistemas Neurossecretores/virologia , Infecções por Orthomyxoviridae/mortalidade , Sistema Hipófise-Suprarrenal/imunologia , Sistema Hipófise-Suprarrenal/virologia , Estresse Fisiológico/imunologia , Análise de Sobrevida
15.
J Immunol ; 162(8): 4998-5002, 1999 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-10202048

RESUMO

The mechanisms for activating the hypothalamic-pituitary-adrenal (HPA) axis and the roles glucocorticoids play in the pathogenesis of chronic infectious disease are largely undefined. Using the LP-BM5 model of retrovirus-induced immunodeficiency, we found alterations in HPA axis function, manifested as an increase in circulating levels of adrenocorticotropic hormone and corticosterone, beginning after only 3 mo of infection. These changes occurred contemporaneously with a shift in the profile of circulating cytokines from a Th1-dominant (IFN-gamma) to Th2-dominant (IL-4, IL-10) phenotype. No significant changes in either circulating IL-1beta, IL-6, or TNF-alpha levels were observed in infected mice. Administering the N-methyl-D-aspartate receptor antagonist MK-801 to infected mice normalized plasma adrenocorticotropic hormone and corticosterone levels, indicating that glutamate was a major activator of the HPA axis. Moreover, MK-801 treatment of late-stage mice also reversed the type 1 to type 2 cytokine shift to a degree comparable or superior to treatment with the glucocorticoid receptor antagonist RU-486. These findings indicate that HPA axis activation during LP-BM5 retrovirus infection is mediated by the chronic hyperactivation of glutamatergic pathways in the hypothalamus. Through this mechanism, the degree of peripheral immunodeficiency observed in the late-stage disease is profoundly augmented.


Assuntos
Adjuvantes Imunológicos/farmacologia , Ácido Glutâmico/fisiologia , Sistema Hipotálamo-Hipofisário/imunologia , Síndromes de Imunodeficiência/imunologia , Vírus da Leucemia Murina/imunologia , Sistema Hipófise-Suprarrenal/imunologia , Animais , Citocinas/sangue , Citocinas/fisiologia , Maleato de Dizocilpina/administração & dosagem , Ácido Glutâmico/imunologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/virologia , Síndromes de Imunodeficiência/metabolismo , Síndromes de Imunodeficiência/fisiopatologia , Bombas de Infusão , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/virologia , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores
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