Paratrygon aiereba irradiated anti-mucus serum reduce edematogenic activity induced in experimental model.

Accidents by freshwater stingrays are common in northern Brazil, there is no specific therapy for high morbidity and local tissue destruction. The irradiation of venoms and toxins by ionizing radiation has been used to produce appropriate immunogens for the production of antisera. We planned to study the efficacy of stinging mucus irradiation in the production of antisera, with serum neutralization assays of edematogenic activity and quantification of cytokines performed in animal models of immunization with native and irradiated mucus of Paratrygon aiereba, a large freshwater stingray. Antiserum potency and its cross-reactivity with mucus from other freshwater stingrays were detected by ELISA. Immunization models demonstrated the ability to stimulate a strong humoral response with elevated levels of serum IgG detectable by ELISA, and both native and irradiated mucus were immunogenic and capable of recognizing mucus proteins from other freshwater neotropical stingrays. Mucus P. aiereba causes cellular and humoral adaptive immune responses in cells of immunized mice producing antibodies and cytokines such as TNF-α, IL-6 and IL-17. Rabbit antisera immunized with mucus from P. aiereba irradiated at 2 kGy showed a significant reduction of mucus-induced edematogenic activity in mice. Our data suggest that the use of antisera against freshwater stingray mucus show the possibility of specific therapy for these accidents.

Beta-Adrenergic Blockade Decreases the Neuroimmune Changes in Mice Induced by Cohabitation with an Ehrlich Tumor-Bearing Cage Mate.

OBJECTIVES: Cohabitation with Ehrlich tumor-bearing (ETB) mice induced behavioral, neurochemical, hormonal, and immune effects in the conspecifics as a consequence of stress-induced activation of the sympathetic nervous system (SNS) with catecholamine release. In the current study, the nonspecific ß-AR blocker d,l-propranolol and the specific ß2-AR blocker ICI-118.551 were employed as pharmacological tools to assess the extent to which catecholamines participated in the effects induced by cohabitation with ETB mice. METHODS: Two experiments were performed, 1 with d,l-propranolol treatment and the other with ICI-118.551. One mouse in the experimental group was called the "companion of the sick partner" (CSP) since it was forced to live in the same cage with 2 (experiment 1) or 1 (experiment 2) cage mate that had been i.p. injected with 5 × 106 Ehrlich tumor cells. RESULTS: The d,l-propranolol treatment, but not the ICI-118.551 treatment, attenuated the effects of cohabitation with 2 ETB mice on both open-field behavior and the hypothalamic levels and turnover rate of norepinephrine. The 2 ß-AR blockers were unable to change the serum corticosterone levels and adrenal weights of the CSP mice; however, these drugs abrogated the effects of cohabitation on neutrophil oxidative burst and phagocytosis. Finally, an increase in the 5-HT turnover rate was observed in the olfactory bulb of CSP mice compared to their respective controls, an effect that was not modified by ß-AR blockade. CONCLUSION: These results confirm and strengthen our hypothesis that the SNS is involved in the effects induced by cohabitation with ETB mice and point towards ß2-AR participation in the immune effects analyzed.

Odor cues released by Ehrlich tumor-bearing mice are aversive and induce psychological stress.

BACKGROUND/AIMS: This study aimed to verify if odor cues released by Ehrlich tumor-bearing mice are aversive and stressful. METHODS: Female mice were divided into a control group and an experimental group. One animal of each experimental pair of mice was inoculated with 5 × 10(6) Ehrlich tumor cells intraperitoneally; the other animal was kept undisturbed and was referred to as a CSP (companion of sick partner). One mouse of each control pair was treated intraperitoneally with 0.9% NaCl (1 mg/kg); the other animal (CHP, companion of healthy partner) was kept undisturbed. RESULTS: It was shown that, in relation to CHP, CSP mice (1) spent less time within the companion zone in a T-maze place preference test, (2) had increased levels of social interaction, (3) had increased levels of plasmatic adrenaline and noradrenaline and (4) displayed no changes in serum corticosterone levels before and after an immobilization stress challenge. It was also shown that (5) cohabitation with 2 tumor-bearing mice was more effective in decreasing neutrophil oxidative burst than cohabitation with 1 sick partner and (6) the presence of a healthy conspecific within the cage of the tumor-injected/CSP pair abrogated the effects of cohabitation on neutrophil activity. These results show that odor cues released by Ehrlich tumor-injected mice are aversive and induce psychological stress. CONCLUSION: We postulate that the aversive response induced by the chemosignals released by Ehrlich tumor-injected animals activates the sympathetic nervous system and causes the neuroimmunal changes that occur in the mice cohabiting with the sick mice.

Lipopolysaccharide-induced sickness behavior in lactating rats decreases ultrasonic vocalizations and exacerbates immune system activity in male offspring.

OBJECTIVE: The present study analyzed the effects of lipopolysaccharide (LPS) on maternal behavior during lactation and possible correlations with changes in emotional and immune responses in offspring. METHODS: Lactating rats received 100 µg/kg LPS, and the control group received saline solution on lactation day (LD) 3. Maternal general activity and maternal behavior were observed on LD5 (i.e. the day that the peak of fever occurred). In male pups, hematological parameters and ultrasonic vocalizations (USVs) were assessed on LD5. At weaning, an additional dose of LPS (50 µg/kg, i.p.) was administered in male pups, and open-field behavior, oxidative burst and phagocytosis were evaluated. RESULTS: A reduction in the time in which dams retrieved the pups was observed, whereas no effects on maternal aggressive behavior were found. On LD5, a reduction of the frequency of USVs was observed in pups, but no signs of inflammation were found. At weaning, an increase in immune system activity was observed, but no differences in open-field behavior were found. CONCLUSION: These results indicate that inflammation in lactating mothers disrupted mother/pup interactions and may have produced short- and long-term effects on pup behavior as well as biological pathways that modulate inflammatory responses to bacterial endotoxin challenge in pups.

Neuroimmune interactions and psychologycal stress induced by cohabitation with a sick partner: a review.

This study reviews the neuroimmunological consequences elicited in mice from long-term cohabitation with tumor-bearing conspecifics. Two types of experiments were performed; one used Swiss female mice and Ehrlich tumor cells, and the other used C57Bl/6 female mice and B16F10 melanoma cells. The female Swiss mice and the C57Bl/6 mice were divided into two groups, i.e., control and experimental. One mouse in each control pair was treated with control solutions (1.0 mL/kg); the other was kept undisturbed and called the 'companion of health partner' (CHP). One mouse in each experimental pair was inoculated with 5 x 10(6) Ehrlich tumor cells or with 10(6) murine B16-F10 melanoma cells; the other mouse, which was the subject of the performed studies, was left undisturbed and called the 'companion of sick partner' (CSP). Although we used two different strains of mice and two different tumor types, the CSP mice presented, in relation to the CHP mice, an increased locomotion in the open field and plus maze apparatuses and no changes in the corticosterone serum levels before and after the immobilization-stress challenge. The Swiss CSP mice showed a reduced level and an increased turnover rate of hypothalamic noradrenaline (NE), as well as increased plasmatic levels of adrenaline and NE. Changes in the immune cell phenotype and activity were also observed in the Swiss and C57Bl/6 CSP mice. The study found that odor cues left by the Ehrlich tumor-injected Swiss mice are aversive and may therefore be responsible for the neuroimmune changes reported in the CSP mice. It is proposed that the final neural link between the neuroimmunological changes observed in the CSP mice involves psychogenic stress imposed by the housing condition and the activation of the brain catecholaminergic pathways and the sympathetic nervous systems.

Odor cues from tumor-bearing mice induces neuroimmune changes.

Cohabitation for 14 days with an Ehrlich tumor-bearing mice was shown, among others, to increase locomotor activity, and hypothalamic noradrenaline levels and turnover, to decrease the innate immune responses and animal resistance to tumor growth. The present experiment was designed to access the relevance of tactile, olfactory, and visual communication to the neuroimmune changes induced by cohabitation with a tumor-bearing partner. Mice that were not allowed to perceive odor cues from their sick partners presented no alterations in neutrophil activity, a fact not observed after visual deprivation and physical isolation. Mice use scents for intraspecies communication in many social contexts. Tumors produce volatile organic compounds released into the atmosphere through breath, sweat, and urine. The present results strongly suggest that volatile compounds released by Ehrlich tumor-injected mice are perceived by their conspecifics, inducing the neuroimmune changes reported for cohabitation with a sick companion.

Depressão, antidepressivos e sistema imune: um novo olhar sobre um velho problema: [revisão] / Depression, antidepressants and immune system: a new look to an old problem: [review]

CONTEXTO: A hipótese monoaminérgica da depressão não responde a uma série de questões, tais como "quais as causas dos distúrbios monoaminérgicos?" e "como explicar uma taxa de 30 por cento de refratariedade aos antidepressivos?". Sendo assim, outras teorias têm sido propostas, entre elas, aquelas que enfocam as participações dos sistemas imune e endócrino. OBJETIVOS: Analisar criticamente o papel do sistema de resposta imunoinflamatória na depressão e discutir a interação dos antidepressivos com esse sistema, tanto do ponto de vista básico como clínico. MÉTODOS: Realizou-se pesquisa bibliográfica utilizando-se as bases de dados MedLine e SciELO. RESULTADOS: Pacientes vítimas de estresse crônico e depressão apresentam ativação das respostas imunoinflamatórias e do eixo hipotálamo-hipófise-adrenal, os quais, direta ou indiretamente, influenciam a neurotransmissão. Nesse sentido, a utilização de antidepressivos não apenas aumenta a disponibilidade de neurotransmissores na fenda sináptica, mas também induz mudança do padrão de resposta imune Th1 - pró-inflamatório - para o Th2, que é antiinflamatório. Além disso, sabe-se que pacientes não responsivos aos antidepressivos possuem o sistema imuneinflamatório mais ativo. No entanto, há uma série de dados controversos na literatura, havendo indícios de um perfil imune diferente de acordo com o tipo de depressão. CONCLUSÕES: A compreensão de aspectos neuroimunes presentes na depressão poderia contribuir para um melhor entendimento das bases biológicas desse transtorno e, possivelmente, para novas perspectivas na busca de uma terapêutica mais efetiva.

BACKGROUND: The monoaminergic hypothesis of depression does not answer certain questions, such as "what are the causes of the monoaminergic disturbances?" and "how to explain the existence of 30 percent refractory patients to antidepressants?". Therefore, other theories have emerged, such as those focusing on the immune and endocrine systems. OBJECTIVES: To analyze the role of the immune-inflammatory system on depression and, furthermore, the interactions between antidepressants and this system, from basic and clinical points of view. METHODS: Literature review was carried out in the MedLine and SciELO databases. Patients suffering of chronic stress and depression present an activation of both inflammatory responses and hypothalamic-pituitary-adrenal axis, which, directly or indirectly, influence neurotransmission. Therefore, the use of antidepressants not only increases the availability of neurotransmitters in the synaptic cleft, but also changes the pattern of Th1 immune response - pro-inflammatory - to the Th2, which is antiinflammatory. Moreover, it is known that patients who do not respond to antidepressant treatment have hyperactive immune-inflammatory response system. However, there are several controversies in the literature, and evidences suggest a different immune profile according to the type of depression. DISCUSSION: The understanding of the neuroimmune aspects of depression might contribute to a better comprehension of the biological basis of this disorder and, therefore, to a new perspective in the search for a more effective therapy.

Neuroimunomodulação: sobre o diálogo entre os sistemas nervoso e imune / Neuroimmunomodulation: the cross-talk between nervous and immune systems

OBJETIVO: Trabalhos de pesquisa provenientes do campo da neuroimunomodulação vêm tornando explícitas as intrincadas relações existentes entre o sistema nervoso central e o sistema imune. Uma revisão bibliográfica foi realizada com o objetivo de descrever as bases de estudo da neuroimunomodulação. MODELOS EXPERIMENTAIS: Sabe-se, hoje, que estados emocionais como ansiedade e depressão são capazes de modificar a atividade do sistema imune como também o fazem o estresse e fármacos com ação no sistema nervoso central. COMPORTAMENTO DOENTIO: Os comportamentos apresentados por um organismo doente devem ser encarados como decorrência de estratégias homeostáticas de cada indivíduo. POSSÍVEIS MECANISMOS DE SINALIZAÇÃO DO SISTEMA IMUNE PARA O SISTEMA NERVOSO CENTRAL: Grande destaque tem sido atribuído para a participação do eixo hipotálamo-pituitária-adrenal, do sistema nervoso autônomo simpático e das citocinas nas sinalizações entre o sistema nervoso central e o sistema imune. CONCLUSÃO: O presente artigo pretende mostrar a relevância dos fenômenos de neuroimunomodulação; ele faz uma análise crítica das influências do sistema nervoso central sobre o sistema imune e vice-versa.

OBJECTIVE: Several papers arriving from the neuroimmunomodulation field are showing the relevant relationships between the nervous and the immune systems. A review of studies was carried out to describe the bases of the studies on neuroimmunomodulation. EXPERIMENTAL MODELS: It is clear nowadays that emotional states such as anxiety and depression change immune system activity, an affect also observed after both stress and use of nervous system acting drugs. SICK BEHAVIOR: The behavior displayed by sick organisms might be thought as being a consequence of homeostatic strategies. POSSIBLE MECHANISM OF THE ACTION BY MEANS OF IMMUNE SYSTEM TO NERVOUS SYSTEM: A very big emphasis is being given to Hipothalamus-pituitary-adrenal axis, simpathetic nervous system and cytokines participation on nervous system and immune system relationships. CONCLUSION: The present revision intend to show some essential studies in the neuroimmunomodulation field; it makes a critical analysis of the mutual relationships between nervous system and immune system.

[Neuroimmunomodulation: the cross-talk between nervous and immune systems]. / Neuroimunomodulação: sobre o diálogo entre os sistemas nervoso e imune.

OBJECTIVE: Several papers arriving from the neuroimmunomodulation field are showing the relevant relationships between the nervous and the immune systems. A review of studies was carried out to describe the bases of the studies on neuroimmunomodulation. EXPERIMENTAL MODELS: It is clear nowadays that emotional states such as anxiety and depression change immune system activity, an affect also observed after both stress and use of nervous system acting drugs. SICK BEHAVIOR: The behavior displayed by sick organisms might be thought as being a consequence of homeostatic strategies. POSSIBLE MECHANISM OF THE ACTION BY MEANS OF IMMUNE SYSTEM TO NERVOUS SYSTEM: A very big emphasis is being given to Hipothalamus-pituitary-adrenal axis, sympathetic nervous system and cytokines participation on nervous system and immune system relationships. CONCLUSION: The present revision intend to show some essential studies in the neuroimmunomodulation field; it makes a critical analysis of the mutual relationships between nervous system and immune system.

Cohabitation with a sick cage mate: effects on ascitic form of Ehrlich tumor growth and macrophage activity.

The present study was designed to evaluate the effects of mice cohabitation with a sick conspecific cage mate on peritoneal macrophage activity and on resistance to Ehrlich tumor growth. Female mice housed in pairs were divided into control and experimental groups. One mouse of each control pair was inoculated with NaCl (0.1 ml/10 g) intraperitoneally and the other, called 'companion of healthy partner' (CHP), was kept undisturbed. One animal of each experimental pair of mice was inoculated with 5.0 x 10(6) Ehrlich tumor cells intraperitoneally and the other, the subject of this study, was called 'companion of sick partner' (CSP). Peritoneal macrophages were removed from CSP and CHP mice to analyze resident macrophage activity (experiment 1), macrophage activity after Mycobacterium bovis (experiment 2) or Ehrlich tumor cells (experiment 3) in vivo inoculations. The resistance of CSP and CHP mice to Ehrlich tumor growth was also analyzed (experiment 4). Differences between groups were not found on resident macrophage activity. However, Onco-BCG- and Ehrlich tumor-activated macrophages from CSP mice presented a decreased intensity and percentage of phagocytosis and an increased respiratory burst in the presence of Staphylococcus aureus stimulation in vitro. CSP animals at the same time displayed a decreased resistance to Ehrlich tumor growth. These data were discussed in light of a possible psychological stress effect imposed by the housing condition on mice's peritoneal macrophage activity and, as a consequence, on their resistance to Ehrlich tumor growth.

Cohabitation with a sick cage mate: Effects on noradrenaline turnover and neutrophil activity.

The present study was designed to evaluate the effects of cohabitation for 11 days with a sick conspecific on hypothalamic levels and turnover of noradrenaline NA (experiment 1) and on neutrophil oxidative burst and phagocytosis in mice (experiment 2). Female mice were divided into two groups: control and experimental. One mouse of each control pair was kept undisturbed and called "companion of health partner" (CHP). One animal of each experimental pair of mice was inoculated with 5 x 10(6) Ehrlich tumor cells i.p., and the other, the subject of this study, was called "companion of sick partner" (CSP). In experiment 3, CHP and CSP mice were treated with diazepam (1.0 mg/kg) or with control solution (vehicle of diazepam, 1.0 mL/kg) 1h before evaluation of neutrophil activity. The CSP mice presented (1) decreased levels and increased turnover of hypothalamic NA; (2) decreased neutrophil oxidative burst after PMA or Staphylococcus aureus induction; (3) decreased percentage and intensity of neutrophil phagocytosis. In CSP mice, diazepam induced no changes in neutrophil oxidative burst or intensity of phagocytosis, but abolished almost completely the percentage of neutrophils performing phagocytosis. These data were discussed in the light of possible neuroimmune interactions.

Método para avaliar experimentalmente a resposta imune humoral em ovinos / Method for the humoral immune response experimental evaluation in ovine

O objetivo do presente trabalho foi estabelecer um método de titulaçäo de anticorpos em ovinos, experimentalmente imunizados com vacina contra a brucelose, usando uma diluiçäo sérica em progressäo aritmética e checar o melhor momento para se encontrar altos títulos de anticorpos. Cinco ovinos machos sem raça definida, adultos e castrados, foram imunizados com uma vacina comercial de Brucella abortus B 19 e foram coletadas amostras de sangue diariamente durante cinco semanas. Os soros foram diluídos nas seguintes concentraçöes: 1:1, 1:5, 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90 e 1:100 e misturados com um antígeno comercial para diagnóstico da brucelose. A reaçäo positiva da amostra mais diluída foi considerada como o título. Reaçöes positivas só foram encontradas nos dias 3 e 4 e o título médio mais alto foi encontrado no dia 6 (1:72). O título individual mais alto encontrado foi de 1:90. Após o dia 6, o título caiu até o dia 14 mostrando, entäo uma lenta tendência decrescente.(au)