Cytokine levels in euthymic bipolar patients (original) (raw)
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Comparison of Cytokine Levels In Depressed, Manic and Euthymic Patients With Bipolar Disorder
Journal of affective …, 2009
The neurobiology of bipolar disorder is not completely understood. Cytokines have received increasing attention as potential mediators of the interaction with immune, neuroendocrine system and specific pathways involved in mood, energy, and activity control. Previous reports have suggested the association of mania and bipolar depression with a proinflammatory state. However, they did not compare cytokine levels in all phases of bipolar disorder. Methods: Sixty-one bipolar patients were recruited for assessment of serum cytokine levels. Of these, 14 were in euthymic state, 23 and 24 were in manic and depressive episodes, respectively. A healthy comparison group included 25 healthy volunteers. Cytokines involved in Th1/Th2 balance, such as TNF-α, IL-2, IL-4, IL-6, IL-10, IFN-γ, were examined by flow cytometry. Results: During mania, proinflammatory cytokines, IL-2, IL-4 and IL-6, were increased in comparison with healthy subjects. Patients in depressive episode showed only increased IL-6 levels. There were no significant differences in cytokine levels between patients in remission and healthy subjects, except for IL-4. Mood symptoms showed a positive correlation with IL-6 and IL-2. Discussion: These findings suggest that mania, and to a less extent, depression are associated with a proinflammatory state. These changes seem to be related to mood state, as changes in cytokine profile were more pronounced during acute episodes than in euthymia. This study provides further support to investigate the immune system as a target for future treatment development.
Journal of Affective Disorders, 2014
Objective: Inflammatory cytokines have been suggested to be the trait or state markers of bipolar disorder, but with inconsistent results. This may be related to small sample sizes and poor control of some important confounding factors. Methods: Gender/age-matched outpatients with bipolar disorder and normal controls were enrolled. The clinical symptoms were rated using the Montgomery Åsberg Depression Rating Scale and Young Mania Rating Scale. Inflammatory cytokines, including soluble interleukin-6 receptor (sIL-6R), soluble interleukin-2 receptor (sIL-2R), C-reactive protein (CRP), soluble tumor necrosis factor receptor type 1 (sTNF-R1), soluble P-selectin receptor (sP-selectin), and monocyte chemotactic protein-1 (MCP-1), were assessed by enzyme-linked immunosorbent assays. Results: In total, 130 patients with bipolar disorder and 130 normal subjects were enrolled. Among the patients with bipolar disorder, 77 (59.2%) had bipolar I disorder, 53 (40.8%) had bipolar II disorder; 75 (57.7%) were in a euthymic state, 14 (10.8%) were in a manic/hypomanic state, and 41 (31.5%) were in a depressive state. The 130 bipolar patients had significantly higher levels of all cytokines than the normal controls (all po 0.0001). Using multivariate regression analysis with controlling of age, gender, BMI, smoking, duration of illness, and medication grouping, the patients with bipolar II disorder had significantly lower levels of sTNF-R1 than the patients with bipolar I disorder (p¼ 0.038); the patients in a depressive state had significantly lower levels of sTNF-R1 than the patients in manic/hypomanic and euthymic states (p¼ 0.009). Conclusion: The study supported the association of bipolar disorder with inflammatory dysregulation, and sTNF-R1 may be a potential biomarker for staging bipolar disorder.
Immunologic variables in acute mania of bipolar disorder
Journal of Neuroimmunology, 2004
Macrophages, lymphocytes and their products, may be involved in the pathophysiology of psychiatric disorders. The cell-mediated immune activation response of manic patients during pre-medication and medication stages remains unclear. The purpose of this case-control study was to investigate the plasma levels of immunologic variables, including interleukin (IL)-1 receptor antagonist (IL-1RA), soluble CD 4 (sCD4) and sCD8, and TH1 (interferon [IFN]-g and IL-2) and TH2 (IL-4 and IL-10) cytokines in patients with pre-medicated, medicated bipolar mania. The study subjects, aged 16-44 years, were physically healthy patients with Young Mania Rating Scale (YMRS) scores z 26, and normal controls, aged 19-40 years, were matched for sex. The immune variables were measured in acute mania and in consequent remission (YMRS scores V 12) among bipolar patients. The plasma levels of IL-1RA, sCD4, and sCD8 were found significantly increased in pre-medicated acute manic patients as compared to normal controls. But only IL-1RA and sCD8 were found different in remitted bipolar patients as compared to normal controls. For TH1 cytokines, culture supernatant level of IFN-g was found significantly lower in manic patients of both acute and remission stages as compared to normal controls. No significant difference was found in IL-2 level in premedicated acute manic patients compared to controls. For TH2 cytokines, no significant differences in IL-4 and IL-10 levels were observed. We showed that cell-mediated immune response was activated in patients with bipolar disorder during the pre-medication, medication, and the remission stages. Our study findings suggest that the immune-modulation in patients with bipolar disorder may be abnormal.
Imbalance between pro-inflammatory and anti-inflammatory cytokines in bipolar disorder
Journal of Affective Disorders, 2007
Background: The role of cytokines in bipolar disorder is still controversial. Although a few studies have found alterations of cytokines in bipolar disorder, their findings were inconsistent. The aim of this study was to determine whether the cytokines are involved in the pathophysiology of bipolar disorder. Methods: A total of 37 manic patients with bipolar disorder and 74 control subjects were recruited. The mitogen-induced production of tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6), IL-4, interferon (IFN)-gamma, and IL-2 was measured using quantitative sandwich ELISA at the time of admission and 6 weeks after mood stabilizer treatment. Results: IL-6 and TNF-alpha production of bipolar manic patients was significantly higher than those of normal controls, while IL-4 values of the patients were significantly lower than normal controls. IL-6/IL-4, TNF-alpha/IL-4, IL-2/IL-4, and IFN-gamma/IL-4 ratios were significantly higher in bipolar manic patients than in normal controls. After 6 weeks of treatment, the levels of IL-6 significantly decreased compared with baseline. Limitations: The effect of various types of mood stabilizers on cytokine production should be considered. Conclusions: These findings suggest that the increased activity of pro-inflammatory cytokines and an imbalance between proinflammatory and anti-inflammatory cytokines may play a role in the pathophysiology of bipolar disorder.
Cytokine profiles in bipolar affective disorder: Focus on acutely ill patients
Journal of Affective Disorders, 2006
Background: The role of the immune system in mood disorders is predominately supported by studies in unipolar major depression. However activation of the immune system has also been demonstrated in bipolar mania. Our study examines proinflammatory and anti-inflammatory cytokines in both phases of bipolar affective disorder (BPAD). Methods: Plasma concentrations of IL-6, IL-8, IL-10, TNF-a and sIL-6R were measured with enzyme linked immunosorbent assays (ELISA) in patients with BPAD who were depressed, or manic and in healthy controls. Results: Bipolar depression had significantly higher production of the pro-inflammatory cytokines, IL-8 ( p b 0.001) and TNF-a ( p b 0.05) compared to healthy subjects. The manic group also had increased production of IL-8 ( p b 0.05) and TNF-a ( p b 0.001) as compared to healthy subjects. Anti-inflammatory cytokine levels did not differ across the 3 groups.
Immuno- inflammatory markers of bipolar disorder: a review of evidence
Frontiers in Bioscience, 2012
Introduction 3. Immuno-inflammatory markers in bipolar disorder 3.1. Abnormalities of the innate and the adaptative system in bipolar disorder 3.2. C-reactive protein (crp) and bipolar disorder 3.3. Autoimmunity in bipolar disorder 3.4. The contribution of immunogenetics in bipolar disorder 4. The viral hypothesis 4.1. A winter/spring excess of birth in bipolar disorder 4.2. Viruses and bipolar disorder 5. The retroviral hypothesis: a new avenue of research? 6.
Bipolar disorders, 2015
Abnormalities of protein levels of proinflammatory cytokines and their soluble receptors have been reported in plasma of patients with bipolar disorder (BP). In this study, we tested the hypothesis that the mRNA expression of membrane-bound receptors for proinflammatory cytokines will be altered in the lymphocytes of patients with BP. We determined protein and mRNA expression of proinflammatory cytokines, and mRNA expression of their receptors in the lymphocytes from 29 drug-free, hospitalized patients with BP and 30 drug-free normal control subjects. The subjects were diagnosed according to DSM-IV criteria. Plasma protein levels of cytokines were determined by enzyme-linked immunosorbent assay (ELISA); mRNA levels in lymphocytes were determined by the quantitative polymerase chain reaction (qPCR) method. We found that mean mRNA levels of the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and their receptors TNFR1, IL-1R1, and the antagonist I...
Proliferation and apoptosis of T lymphocytes in patients with bipolar disorder
Scientific Reports, 2018
The aim of the study was to evaluate proliferation capacity and susceptibility to apoptosis of T lymphocytes of patients with bipolar disorder (BD) and to investigate in vitro influence of two standard mood stabilizers: lithium and valproic acid on these parameters using flow cytometry. Our results show that T lymphocytes of BD patients, especially those treated with lithium, have reduced proliferation capacity compared to healthy people. In vitro studies showed that valproic acid reduces the number of cell divisions and percentages of proliferating cells regardless of health status but mainly in very high dose, while lithium has no significant influence on proliferation capacity of patients' T lymphocytes. Lymphocytes of BD patients are also more prone to apoptosis compared with healthy individuals which is related to high expression of Bax, a pro-apoptotic protein. In vitro lithium protected patients' lymphocytes from apoptosis proportionally to dose used. Valproic acid protected lymphocytes of patients from apoptosis mainly in therapeutic concentration. Our results show that mood stabilizers used to prevent relapses of the disease have anti-apoptotic effect on T lymphocytes of BD patients but they are not able to improve their proliferation capacity. Bipolar disorder (BD) is a serious mental illness with cyclic alternations of mood. It can have a form of depressive and manic episodes in BD type I or depressive and hypomanic episodes in type II but other subtypes and forms of bipolar disorder known as "bipolar spectrum" have been also described 1. Presently, BD is recognized as a multisystem condition affecting not only patient's mood and behavior but also endocrine and immune system. In addition to several severe medical conditions accompanying BD, like cardiovascular and metabolic diseases, attention is also being paid to immune dysfunction. This is due to the fact that BD patients are more likely to suffer from cancer 2 and autoimmune diseases 3. Moreover, some authors suggest that there is association between immune findings and mood episodes. Thorough investigation of the dysfunction of the immune system in BP is believed to be a key to finding biomarkers that would allow to predict disease progression and even help in treatment selection. Presently, most of the studies focus mainly on changes in cytokine concentrations in BD. Different authors seem to agree that there is imbalance between pro-and anti-inflammatory cytokines 4-6. Kim et al. have shown that mitogen-induced production of tumor necrosis alpha (TNF-α) and interleukin 6 (IL-6) is significantly higher in bipolar manic patients compared to healthy people 4. Pandey et al. confirmed abnormally high gene expression of pro-inflammatory cytokines and their receptors in lymphocytes isolated from patients with BD 5. Comparison of cytokine levels in depressed and manic patients revealed that during manic phase there is an increase in the concentration of cytokines such as IL-2, IL-4, IL-6 compared to healthy people, whereas in depressive episode only the level of IL-6 is increased 6. Breunis et al. have demonstrated that bipolar disorder is accompanied by high numbers of circulating activated (CD25 +) T cells and raised levels of interleukin-2 receptors (sIL-2Rs) compared to healthy control 7 , while Tsai et al. showed that increase of sIL-2Rs is higher in patients with acute mania compared to patients in remission 8. Other authors also demonstrated decrease of interferon gamma (INF-γ) production in acute mania and in subsequent remission compared to healthy people 9. Changes in the cytokine production could be associated with impaired proliferative responses of T lymphocytes to stimulation, changes in the expression of surface antigens or increased susceptibility to apoptosis.