RESUMO
It is well established that the hypothalamic-pituitary-adrenal responses to immune stressors are sexually dimorphic in rodents (females > males), but the underlying mechanism is still unclear. To investigate the mechanism, in this study we examined whether the sex steroid environment affects the following variables in male and female rats: (1) plasma levels of ACTH, interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) after systemic lipopolysaccharide (LPS) administration; (2) static concentrations of corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) in the mediobasal hypothalamus (MBH) and those of ACTH in the anterior pituitary (AP); and (3) the binding characteristics of IL-1beta, IL-6 and TNF-alpha in the MBH and AP. LPS-induced ACTH release was significantly higher in female than in male rats, and this sexual difference was abolished by performing gonadectomy in both sexes. Administration of physiological doses of testosterone and oestradiol to gonadectomized males and females, respectively, restored the altered ACTH responses to normal. Changes in the sex steroid milieu did not affect plasma cytokine responses to LPS, tissue contents of CRH, AVP and ACTH, or the IL-6 binding characteristics in the MBH and AP. However, the number of IL-1beta and TNF-alpha binding sites, but not their binding affinities, in the MBH showed significant changes according to altered sex hormone milieu, in the same direction as the LPS-induced ACTH response. These results suggest that the hypothalamic sensitivity to peripheral IL-1beta and TNF-alpha may be an important mechanism underlying the sexually dimorphic ACTH response to LPS in rats.
Assuntos
Citocinas/metabolismo , Estrogênios/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Hipotálamo Anterior/metabolismo , Hipotálamo Médio/metabolismo , Caracteres Sexuais , Testosterona/metabolismo , Hormônio Adrenocorticotrópico/sangue , Animais , Arginina Vasopressina/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Estrogênios/farmacologia , Feminino , Hormônios Esteroides Gonadais/farmacologia , Hipotálamo Anterior/efeitos dos fármacos , Hipotálamo Anterior/imunologia , Hipotálamo Médio/efeitos dos fármacos , Hipotálamo Médio/imunologia , Interleucina-1/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Masculino , Orquiectomia , Ovariectomia , Ratos , Ratos Wistar , Testosterona/farmacologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The effects of interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) perfused locally into the anterior hypothalamus (AHY) on serotonin (5-hydroxytryptamine, 5-HT) release were investigated in the same region using in vivo microdialysis in conscious, freely moving F344 rats. IL-1beta (1 ng/rat) or IL-6 (50 ng/rat) injected directly into the AHY elicited a rapid and transient statistically significant increase in extracellular 5-HT levels (to 161% and 145% of the respective AUC (area under the curve) basal value, 100%). Intra-hypothalamic infusion of IL-1-receptor antagonist IL-1Ra (2 mug/rat) prevented this effect of IL-1beta, but not that of IL-6, suggesting an IL-1beta-independent mechanism for hypothalamic 5-HT release by this latter cytokine. Furthermore, intra-hypothalamic co-perfusion of IL-6 with IL-1beta at sub-optimal doses (10 ng/rat and 0.5 ng/rat, respectively) synergized in releasing hypothalamic 5-HT, thus providing in vivo evidence that both cytokines, IL-6 and IL-1beta are able to modulate the neuronal 5-HT response in the rat AHY.
Assuntos
Hipotálamo Anterior/fisiologia , Interleucina-1/farmacologia , Interleucina-6/farmacologia , Serotonina/metabolismo , Animais , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Hipotálamo Anterior/efeitos dos fármacos , Hipotálamo Anterior/imunologia , Infusões Parenterais , Proteína Antagonista do Receptor de Interleucina 1 , Interleucina-1/administração & dosagem , Interleucina-6/administração & dosagem , Cinética , Masculino , Microdiálise , Ratos , Ratos Endogâmicos F344 , Receptores de Interleucina-1/antagonistas & inibidores , Sialoglicoproteínas/administração & dosagem , Sialoglicoproteínas/farmacologiaAssuntos
Bacteriemia/imunologia , Ventrículos Cerebrais/imunologia , Febre/fisiopatologia , Hipotálamo Anterior/imunologia , Receptores de Interleucina-1/fisiologia , Sialoglicoproteínas/farmacologia , Animais , Bacteriemia/fisiopatologia , Regulação da Temperatura Corporal , Ventrículos Cerebrais/efeitos dos fármacos , Ventrículos Cerebrais/fisiopatologia , Febre/etiologia , Humanos , Hipotálamo Anterior/efeitos dos fármacos , Injeções Intraventriculares , Proteína Antagonista do Receptor de Interleucina 1 , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Interleucina-1/antagonistas & inibidores , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Sialoglicoproteínas/administração & dosagemAssuntos
Infecções Bacterianas/imunologia , Febre/imunologia , Hipotálamo Anterior/imunologia , Interleucina-6/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Animais , Infecções Bacterianas/fisiopatologia , Temperatura Corporal , Febre/etiologia , Hipotálamo Anterior/fisiopatologia , Interleucina-6/sangue , Masculino , Peritonite/imunologia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The effect of destruction of the anterior hypothalamus (AHT) on the immune system was examined in rats 4-50 weeks after the treatment. The thymic weight significantly increased in the experimental group regardless of age, while a significant decrease was observed in the percentage of splenic T cells as well as their proliferative response to phytohemagglutinin (PHA). The increase of thymic weight was observed as long as 24 weeks and the decrease of splenic T cell number was observed as long as 50 weeks after the operation. Hypophysectomy gave rise to atrophy of both thymus and spleen, while either adrenalectomy or gonadectomy resulted in hypertrophy of both thymus and spleen. The results taken together suggest that development and aging of the immune system are under the balance of positive and negative signals from AHT.
Assuntos
Envelhecimento/imunologia , Envelhecimento/patologia , Hipotálamo Anterior/patologia , Terapia de Imunossupressão , Baço/imunologia , Linfócitos T/imunologia , Timo/patologia , Animais , Peso Corporal , Contagem de Células , Feminino , Hiperplasia , Hipotálamo Anterior/imunologia , Hipotálamo Anterior/cirurgia , Ativação Linfocitária/efeitos dos fármacos , Tecido Linfoide/imunologia , Tecido Linfoide/patologia , Tamanho do Órgão , Fito-Hemaglutininas/farmacologia , Ratos , Ratos Wistar , Baço/citologia , Linfócitos T/citologiaRESUMO
We reported previously that a single systemic injection of morphine (10 mg/kg) to rats profoundly suppressed mitogen-induced proliferation of blood lymphocytes by a receptor-mediated mechanism. The present study examined whether this immunosuppressive effect of morphine is mediated by opioid receptors located at either peripheral or central sites. First, the effects of systemic morphine administration on analgesia, mitogen-stimulated lymphocyte proliferation and corticosterone secretion were compared to those observed after the systemic administration of N-methylmorphine, a quaternary derivative which does not readily penetrate the blood-brain barrier. In contrast to systemically administered morphine, the i.p. injection of N-methyl-morphine (20 mg/kg) was without any effect on lymphocyte proliferation, plasma corticosterone concentrations or analgesic responses. Secondly, the effects of morphine and N-methylmorphine after central administration were compared. Within 2 hr after the microinjection of either morphine (10 micrograms/2 microliters) or N-methylmorphine (15 micrograms/2 microliters) into the third ventricle, blood lymphocyte responses were inhibited by 70%, plasma corticosterone concentrations were significantly elevated and maximal analgesic responses were present. Finally, microinjection of morphine (1 microgram/0.2 microliter) into the anterior hypothalamus inhibited blood lymphocyte proliferation by 50% without producing analgesia or a significant increase in plasma corticosterone. These findings suggest that central opioid pathways are involved in the immunosuppressive effects of morphine and these pathways may be distinct from those participating in opioid-induced analgesia and adrenal activation.
Assuntos
Ventrículos Cerebrais/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Tolerância Imunológica/efeitos dos fármacos , Tolerância Imunológica/fisiologia , Morfina/toxicidade , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Animais , Ventrículos Cerebrais/imunologia , Codeína/toxicidade , Concanavalina A/farmacologia , Corticosterona/sangue , Sistema Hipotálamo-Hipofisário/imunologia , Hipotálamo Anterior/efeitos dos fármacos , Hipotálamo Anterior/imunologia , Imunidade Celular/efeitos dos fármacos , Imunidade Celular/imunologia , Injeções Subcutâneas , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Masculino , Microinjeções , Medição da Dor/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/imunologia , Ratos , Ratos Sprague-Dawley , Receptores Opioides/efeitos dos fármacos , Receptores Opioides/fisiologia , Sensibilidade e Especificidade , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologiaRESUMO
The localization and morphology of neurons, processes, and neuronal groups in the rat preoptic area and hypothalamus containing substance P-like immunoreactivity were studied with a highly selective antiserum raised against synthetic substance P. The antiserum was thoroughly characterized by immunoblotting; only substance P was recognized by the antiserum. Absorption of the antiserum with synthetic substance P abolished immunostaining while addition of other hypothalamic neuropeptides had no effect on the immunostaining. The specificity of the observed immunohistochemical staining pattern was further confirmed with a monoclonal substance P antiserum. The distribution of substance P immunoreactive perikarya was investigated in colchicine-treated animals, whereas the distribution of immunoreactive nerve fibers and terminals was described in brains from untreated animals. In colchicine-treated rats, immunoreactive cells were reliably detected throughout the preoptic area and the hypothalamus. In the preoptic region, labeled cells were found in the anteroventral periventricular and the anteroventral preoptic nuclei and the medial and lateral preoptic areas. Within the hypothalamus, immunoreactive cells were found in the suprachiasmatic, paraventricular, supraoptic, ventromedial, dorsomedial, supramammillary, and premammillary nuclei, the retrochiasmatic, medial hypothalamic, and lateral hypothalamic areas, and the tuber cinereum. The immunoreactive cell groups were usually continuous with adjacent cell groups. Because of the highly variable effect of the colchicine treatment, it was not possible to determine the actual number of immunoreactive cells. Mean soma size varied considerably from one cell group to another. Cells in the magnocellular subnuclei of the paraventricular and supraoptic nuclei were among the largest, with a diameter of about 25 microns, while cells in the supramammillary and suprachiasmatic nuclei were among the smallest, with a diameter of about 12 microns. Immunoreactive nerve fibers were found in all areas of the preoptic area and the hypothalamus. The morphology, size, density, and number of terminals varied considerably from region to region. Thus, some areas contained single immunoreactive fibers, while others were innervated with such a density that individual nerve fibers were hardly discernible. During the last decade, knowledge about neural organization of rodent hypothalamic areas and mammalian tachykinin biochemistry has increased substantially. In the light of these new insights, the present study gives comprehensive morphological evidence that substance P may be centrally involved in a wide variety of hypothalamic functions. Among these could be sexual behavior, pituitary hormone release, and water homeostasis.
Assuntos
Hipotálamo/metabolismo , Área Pré-Óptica/metabolismo , Substância P/metabolismo , Animais , Especificidade de Anticorpos , Western Blotting , Colchicina/farmacologia , Reações Cruzadas , Dendritos/imunologia , Dendritos/metabolismo , Homeostase/fisiologia , Região Hipotalâmica Lateral/anatomia & histologia , Região Hipotalâmica Lateral/imunologia , Região Hipotalâmica Lateral/metabolismo , Hipotálamo/imunologia , Hipotálamo Anterior/anatomia & histologia , Hipotálamo Anterior/imunologia , Hipotálamo Anterior/metabolismo , Imuno-Histoquímica , Masculino , Corpos Mamilares/anatomia & histologia , Corpos Mamilares/imunologia , Corpos Mamilares/metabolismo , Área Pré-Óptica/imunologia , Ratos , Ratos Endogâmicos , Substância P/imunologia , Núcleo Supraquiasmático/anatomia & histologia , Núcleo Supraquiasmático/imunologia , Núcleo Supraquiasmático/metabolismoRESUMO
The development of experimental autoimmune encephalomyelitis (EAE) was prevented in rats immunized with encephalitogenic antigen two weeks, but not twelve weeks, after stereotaxic electrolytic destruction of the anterior hypothalamus. Serum antibody level to the antigen myelin basic protein was decreased, and in vitro lymphocyte transformation response to a mitogen was increased. On the other hand, incidence and intensity of chronic experimental autoimmune myasthenia gravis (EAMG) induced by acetylcholine receptor immunization were higher in rats with anterior hypothalamic lesion. In addition, expression of EAE in rats was inhibited when dopamine and norepinephrine in brain were depleted due to intraventricular injection of 6-hydroxydopamine or subcutaneous injection of reserpine. The study indicates hypothalamic modulatory effects on autoimmune response as well as possible involvement of neurotransmitters in this kind of neuroimmunomodulation.
Assuntos
Encefalomielite Autoimune Experimental/imunologia , Hipotálamo Anterior/imunologia , Ativação Linfocitária , Miastenia Gravis/imunologia , Animais , Autoanticorpos/análise , Feminino , Proteína Básica da Mielina/imunologia , Ratos , Ratos Endogâmicos Lew , Receptores Colinérgicos/imunologiaRESUMO
Bilateral electrical lesions were performed in the anterior hypothalamus (AH) and hippocampus (HC) of female Lewis rats. AH but not HC lesions were found to inhibit the appearance of clinical signs typical of experimental allergic encephalomyelitis (EAE). The incidence of EAE was 17.2% and the duration was 1.33 +/- 0.07 days after AH lesions compared with an incidence of 85% and duration of 4.81 +/- 0.6 days in the controls. Destruction of the AH was followed by decreased levels of antibodies to myelin basic protein and increased reactivity of splenic lymphocytes to concanavalin A, but did not affect the extent of mononuclear cell infiltration within the brain and spinal cord.
Assuntos
Encefalomielite Autoimune Experimental/imunologia , Hipotálamo Anterior/imunologia , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/fisiopatologia , Encefalomielite Autoimune Experimental/fisiopatologia , Feminino , Hipotálamo Anterior/fisiopatologia , Ratos , Ratos Endogâmicos LewRESUMO
Immunocytochemical methods were used to compare the localization of somatostatin (SRIF) in the human and rhesus monkey hypothalamus. The distribution of SRIF-containing cell bodies and fibers is similar in the two species. Perikarya are located predominantly in the periventricular region and to a lesser extent in the ventromedial nucleus. Fibers occur in dense clusters within the periventricular region, ventromedial nucleus, arcuate nucleus, median eminence, and pericommissural area of both species. Analysis of serial sections suggests that fibers originate from cells in the periventricular region, extend ventrally through the ventromedial and arcuate nuclei to terminate around the portal vessels of the infundibular stalk, and thereby participate in the regulation of anterior pituitary function. Somatostatinergic fibers are also found surrounding non-immunoreactive perikarya in the ventromedial nucleus and periventricular region of both primates. This arrangement may support somatostatin's postulated role as a neurotransmitter or neuromodulator. The strong similarity between the localization of hypothalamic SRIF in the human and rhesus monkey supports the use of the rhesus monkey as a model for the study of somatostatin as a neuroendocrine regulatory in the human.
Assuntos
Hipotálamo/imunologia , Somatostatina/análise , Adulto , Animais , Axônios/imunologia , Feminino , Histocitoquímica , Humanos , Hipotálamo Anterior/imunologia , Imunoquímica , Macaca mulatta , Masculino , Pessoa de Meia-Idade , Somatostatina/imunologiaRESUMO
Rats with bilateral electrolytic lesions of specific limbic nuclei show alterations in lymphoid cell number and in lymphocyte activation induced in vitro by concanavalin A (Con A). The number of splenocytes decreases after lesioning in the anterior hypothalamus (p less than 0.001), ventromedial hypothalamus (p less than .0.2), and mamillary bodies (p less than. 0.001). The number of thymocytes decreases after lesioning of the anterior hypothalamus (p less than 0.001) and increases after hippocampal lesioning (p less than 0.001). Spleen cell responsiveness to con A decreases subsequent to lesioning of the anterior hypothalamus, whereas reactivity was enhanced after lesion placement in the mamillary bodies (p less than 0.002), hippocampus (p less than 0.001), and amygdaloid complex (p less than 0.001). Thymocyte mitogen reactivity is increased by lesions of the hippocampus (p less than 0.001) and amygdaloid complex (p less than 0.001). These effects manifest themselves maximally 4 days after lesioning, with a return to normal by day 14. These preliminary data indicated that quantitative and qualitative lymphocyte functions are altered by ablation of selected brain nuclei, thereby suggesting the presence of neural modulation of immune function.
Assuntos
Imunidade Celular , Imunocompetência , Sistema Límbico/imunologia , Tonsila do Cerebelo/imunologia , Animais , Hipocampo/imunologia , Hipotálamo Anterior/imunologia , Hipotálamo Médio/imunologia , Contagem de Leucócitos , Ativação Linfocitária , Masculino , Corpos Mamilares/imunologia , Ratos , Ratos Endogâmicos F344RESUMO
The paper is concerned with the effect antibrain antiserum may exert on the activity of succinic dehydrogenase, glutamic dehydrogenase, cytochrome oxidase, and peroxidase. By means of quantitative cytochemistry and electron microscopy it was demonstrated that activity of succinic dehydrogenase activity or cytochrome oxidase increased in the cortex and hypothalamus following the injection of anti-cortex or anti-hypothalamic serum. There were no changes of glutamic dehydrogenase and peroxidase found. Nonspecific alterations of neuronal fine structures were observed in both the cortex and the hypothalamus of rabbits treated with antiserum.
Assuntos
Autoanticorpos/fisiologia , Córtex Cerebral/imunologia , Hipotálamo Anterior/imunologia , Hipotálamo/imunologia , Oxirredutases/metabolismo , Animais , Córtex Cerebral/enzimologia , Córtex Cerebral/ultraestrutura , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Glutamato Desidrogenase/metabolismo , Hipotálamo Anterior/enzimologia , Hipotálamo Anterior/ultraestrutura , Peroxidases/metabolismo , Coelhos , Succinato Desidrogenase/metabolismoAssuntos
Hipersensibilidade/fisiopatologia , Hipotálamo/imunologia , Anafilaxia/imunologia , Animais , Formação de Anticorpos , Sistema Nervoso Autônomo/fisiopatologia , Mapeamento Encefálico , Testes de Fixação de Complemento , Estimulação Elétrica , Cobaias , Hipersensibilidade Tardia/fisiopatologia , Hipersensibilidade Imediata/fisiopatologia , Hipotálamo Anterior/imunologia , Hipotálamo Médio/imunologia , Hipotálamo Posterior/imunologia , Ovalbumina , Coelhos , RatosRESUMO
The number of plaque-forming cells (PFC) in the spleen of rats immunized with sheep red blood cells after the injury of the anterior or the posterior portions of the medial hypothalamus, and also of the thalamus displayed no significant difference from the number of PFC in the spleen of intact animals. The titres of hemolysing and hemagglutinating antibodies in the animals with injuries of the mid-brain were somewhat lower than in the intact animals. A reduction of the circularing antibodies level was not associated with localization of the foci of injury and apparently served as the sequence of the craniocerebral trauma.
Assuntos
Formação de Anticorpos , Hipotálamo/imunologia , Tálamo/imunologia , Animais , Mapeamento Encefálico , Eritrócitos/imunologia , Hemaglutininas/biossíntese , Proteínas Hemolisinas/biossíntese , Hipotálamo Anterior/imunologia , Hipotálamo Posterior/imunologia , Ratos , Ovinos/imunologiaRESUMO
It has been shown experimentally that psychosocial processes influence the susceptibility to some infections, to some neoplastic processes, and to some aspects of humoral and cell-mediated immune responses. These psychosocial effects may be related to hypothalamic activity. Reviewing the mechanisms that may be involved in the role of the hypothalamus in immune responses indicates that there is no single mediating factor. Various processes may participate, including the autonomic nervous system and neuroendocrine activity. The research reviewed has been limited primarily to a consideration of the effect of hypothalamic lesions on humoral immune responses. There is some evidence (45, 80) indicating that hypothalamic lesions also modify cell-mediated immune responses. Further research is required to evaluate the effect of the hypothalamus on cell-mediated immunity.
Assuntos
Hipotálamo Anterior/imunologia , Hipotálamo/imunologia , Imunidade , Estresse Fisiológico/imunologia , Corticosteroides/farmacologia , Anafilaxia/imunologia , Animais , Aprendizagem da Esquiva/fisiologia , Espasmo Brônquico/imunologia , Espasmo Brônquico/fisiopatologia , Cobaias , Histamina/metabolismo , Histamina/farmacologia , Hipersensibilidade Imediata/imunologia , Imunidade Ativa , Imunidade Celular , Músculo Liso/efeitos dos fármacos , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Anafilaxia Cutânea PassivaRESUMO
The distribution of somatostatin was studied in the rat with an immunoperoxidase technique and rabbit anti-somatostatin. Somatostatinergic neurons were identified in the preoptic and anterior periventricular hypothalamus between the anterior commissure, optic chiasm, and the anterior portion of the ventromedial nucleus.