ABSTRACT
Objective: To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors. Methods: Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals' blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β, IL-10, and inducible nitric oxide synthase [iNOS]) were measured. Results: LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation. Conclusion: Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.
Subject(s)
Animals , Male , Bipolar Disorder/immunology , Disease Models, Animal , Lisdexamfetamine Dimesylate , Lithium/pharmacology , Anti-Inflammatory Agents/pharmacology , Nerve Growth Factors/drug effects , Time Factors , Bipolar Disorder/physiopathology , Bipolar Disorder/chemically induced , Enzyme-Linked Immunosorbent Assay , Lipopolysaccharides/pharmacology , Reproducibility of Results , Cytokines/blood , Treatment Outcome , Rats, Wistar , Brain-Derived Neurotrophic Factor/blood , Nitric Oxide Synthase Type II/blood , Locomotion/drug effectsABSTRACT
OBJECTIVE: Previous reports suggest that cytokines act as potential mediators of the interaction between the immune and neuroendocrine systems, and that a proinflammatory state may be associated with bipolar disorder and schizophrenia. The aim is to compare cytokine levels in both disorders. METHOD: Twenty euthymic bipolar disorder patients, 53 chronic stabilized schizophrenia patients and 80 healthy controls were recruited. Subjects were all non-smokers and non-obese. Cytokines TNF-α, IL-6, and IL-10 were examined by sandwich ELISA. RESULTS: IL-6 levels were increased in schizophrenia patients when compared to controls (p < 0.0001) and euthymic bipolar disorder patients (p < 0.0001). IL-6 levels were no different in controls compared to euthymic bipolar disorder patients (p = 0.357). IL-10 was lower in controls compared to schizophrenia patients (p = 0.001) or to bipolar disorder patients (p = 0.004). There was no significant difference in TNF-α serum levels among the groups (p = 0.284). Gender-based classification did not significantly alter these findings, and no correlation was found between the antipsychotic dose administered and cytokine levels in patients with schizophrenia. DISCUSSION: These findings evidence a chronic immune activation in schizophrenia. Bipolar disorder seems to present an episode-related inflammatory syndrome. Increased anti-inflammatory factor IL-10 in bipolar disorder and schizophrenia suggests different patterns of inflammatory balance between these two disorders. Results further support the need to investigate cytokines as possible biomarkers of disease activity or treatment response.
OBJETIVO: Pesquisas sugerem as citocinas como potenciais mediadores da interação entre os sistemas imune e neuroendócrino, e que existe um estado pró-inflamatório associado com transtorno bipolar e esquizofrenia. O objetivo deste estudo é comparar os níveis de citocinas entre os dois distúrbios. MÉTODO: Vinte pacientes com transtorno bipolar eutímicos, 53 pacientes com esquizofrenia crônica estabilizados e 80 controles saudáveis foram recrutados. Todos os indivíduos eram não-fumantes e não-obesos. As citocinas TNF-α, IL-6 e IL-10 foram examinadas por ELISA sanduíche. RESULTADOS: A IL-6 estava aumentada nos pacientes com esquizofrenia quando comparados aos controles (p < 0,0001) e aos pacientes bipolares eutímicos (p < 0,0001). Os níveis de IL-6 não foram diferentes nos controles em comparação com pacientes com transtorno bipolar eutímicos (p = 0,357). Os níveis de IL-10 foram menores nos controles quando comparados aos pacientes com esquizofrenia (p = 0,001) ou aos bipolares (p = 0,004). Não houve diferença significativa nos níveis séricos de TNF-α entre os grupos (p = 0,284). A separação por sexo não mostrou diferenças significativas e não houve correlação entre a dose de antipsicóticos e os níveis de citocinas em pacientes com esquizofrenia. DISCUSSÃO: Estes resultados evidenciam uma ativação imune crônica na esquizofrenia. O transtorno bipolar parece apresentar um aumento da atividade inflamatória relacionado ao episódio de humor. Níveis maiores de IL-10 no transtorno bipolar e esquizofrenia sugerem diferentes padrões de equilíbrio inflamatório entre esses dois transtornos. Resultados fornecem apoio adicional para a investigação de citocinas como possíveis biomarcadores para a atividade da doença ou resposta ao tratamento.
Subject(s)
Adult , Female , Humans , Male , Bipolar Disorder/blood , Inflammation Mediators/blood , /blood , /blood , Schizophrenia/blood , Tumor Necrosis Factor-alpha/blood , Bipolar Disorder/immunology , Case-Control Studies , Inflammation/blood , Schizophrenia/immunology , SyndromeABSTRACT
OBJETIVO: Pesquisas recentes têm implicado fatores imunes na patogênese de diversos transtornos neuropsiquiátricos. O objetivo do presente trabalho é revisar os trabalhos que investigaram a associação entre transtorno bipolar e alterações em parâmetros imunes. MÉTODOS: Artigos que incluíam as palavras-chave: "bipolar disorder", "mania", "immunology", "cytokines", "chemokines", "interleukins", "interferon" e "tumor necrosis factor" foram selecionados em uma revisão sistemática da literatura. As bases de dados avaliadas foram MedLine e Scopus, entre os anos de 1980 e 2008. RESULTADOS: Foram identificados 28 trabalhos que estudaram alterações imunes em pacientes com transtorno bipolar. Seis artigos investigaram genes relacionados à resposta imune; cinco, autoanticorpos; quatro, populações leucocitárias; 13, citocinas e/ou moléculas relacionadas à resposta imune e seis, leucócitos de pacientes in vitro. CONCLUSÕES: Embora haja evidências na literatura correlacionando o transtorno bipolar a alterações imunes, os dados não são conclusivos. O transtorno bipolar parece estar associado a níveis mais elevados de autoanticorpos circulantes, assim como à tendência à ativação imune com produção de citocinas pró-inflamatórias e redução de parâmetros anti-inflamatórios.
OBJECTIVE: Emerging research has implicated immune factors in the pathogenesis of a variety of neuropsychiatric disorders. The objective of the present paper is to review the studies that investigated the association between bipolar disorder and immune parameters. METHODS: Papers that included the keywords "bipolar to disorder", "mania", "immunology", "cytokines", "chemokines", "interleukins", "interferon" and "tumor necrosis factor" were selected in a systematic review of the literature. The evaluated databases were MedLine and Scopus in the period between 1980 and 2008. RESULTS: Twenty eight works were found. Six studies investigated immune response-related genes; five, auto-antibodies; four, leukocyte population; 13, cytokines and/or immune-related molecules; six, leukocytes in vitro. CONCLUSIONS: Although there is evidence in the literature correlating affective disorders with immune parameters, the results are still inconclusive. Bipolar disorder seems to be associated with increased levels of auto-antibodies as well as with a trend for increased immune activation with production of pro-inflammatory cytokines and reduction of the anti-inflammatory parameters.
Subject(s)
Cytokines , Bipolar Disorder/immunology , Bipolar Disorder/therapy , Databases as Topic , Review Literature as TopicABSTRACT
Se investigaron los niveles séricos de las inmunoglobulinas IgA, IgE, IgG e IgM en 13 pacientes esquizofrénicos y 17 maníacos depresivos. La IgE reportó valores por encima de lo normal en el 86.67% de los casos, la IgM en el 33.67% la IgA en el 23.32%; la IgG reportó valores por debajo de lo normal en el 3.33% de los casos. La esquizofrenia superó discretamente a la psicosis maníaco-depresiva en dichoss porcentajes. Todos los casos de esquizofrenia tuvieron alteraciones de la IgE y el único caso con alteración en la IgG fue esquizofrénicos. Se hipotetiza sobre el probable mecanismo responsable de las alteraciones encontradas