Evidence for an immune response in major depression: A review and hypothesis
ABSTRACT 1.1. This paper reviews recent findings on cellular and humoral immunity and inflammatory markers in depression.2.2. It is shown that major depression may be accompanied by systemic immune activation or an inflammatory response with involvement of phagocytic (monocytes, neutrophils) cells, T cell activation, B cell proliferation, an “acute” phase response with increased plasma levels of positive and decreased levels of negative acute phase proteins, higher autoantibody (antinuclear, antiphospholipid) titers, increased prostaglandin secretion, disorders in exopeptidase enzymes, such as dipeptidyl peptidase IV, and increased production of interleukin (IL)-1β and IL-6 by peripheral blood mononuclear cells.3.3. It is hypothesized that increased monocytic production of interleukins (Il-1β and Il-6) in severe depression may constitute key phenomena underlying the various aspects of the immune and “acute” phase response, while contributing to hypothalamic-pituitary-adrenalaxis hyperactivity, disorders in serotonin metabolism, and to the vegetative symptoms (i.e. the sickness behavior) of severe depression.
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ABSTRACT: Several studies have shown that there is an imbalance between pro-inflammatory and anti-inflammatory cytokines in major depressive disorder (MDD). However, little is known about the role of cytokines in suicide. In the present study, amounts of IL-6, IL-2, IFN-gamma, IL-4, and TGF-beta1 produced by mitogen-stimulated whole blood were measured in 36 MDD patients who had recently attempted suicide, 33 non-suicidal MDD patients, and 40 normal controls. The severity of depression symptoms and suicidal behaviors was evaluated using Hamilton's depression rating scale (HDRS), the Lethality Suicide Attempt Rating Scale (LSARS), and the Risk-Rescue Rating (RRR). Non-suicidal MDD patients had significantly higher IL-6 production than suicidal MDD patients and normal controls (p<0.001). Suicidal MDD patients had significantly lower IL-2 compared with non-suicidal patients and normal controls (p<0.001). Both MDD groups, with or without attempted suicide, had significantly lower IFN-gamma and IL-4 and higher TGF-beta1 production. HDRS scores had significant positive correlations with IL-6, IFN-gamma, and the Th1/Th2 ratio and significant negative correlations with IL-4 in non-suicidal depression patients (p<0.005); however, these correlations did not hold true for suicidal patients. Suicidal MDD patients had no significant correlations between the LSARS or RRR scores and cytokine release. Our findings suggest that the immune response has distinct differences between non-suicidal patients and suicidal patients. Non-suicidal MDD may be associated with increased IL-6 production and a Th1/Th2 imbalance with a shift to Th1, while suicidal MDD may be associated with decreased IL-2.Progress in Neuro-Psychopharmacology and Biological Psychiatry 02/2008; 32(2):356-61. DOI:10.1016/j.pnpbp.2007.08.041 · 4.03 Impact Factor
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ABSTRACT: 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. 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. 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. The effect of various types of mood stabilizers on cytokine production should be considered. These findings suggest that the increased activity of pro-inflammatory cytokines and an imbalance between pro-inflammatory and anti-inflammatory cytokines may play a role in the pathophysiology of bipolar disorder.Journal of Affective Disorders 01/2008; 104(1-3):91-5. DOI:10.1016/j.jad.2007.02.018 · 3.71 Impact Factor
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ABSTRACT: One potential pathway by which depression may impact health is through modulation of immune function. Depressed individuals have been shown to display reductions in measures of cellular immune competence as well as elevated markers of systemic inflammation. The current study assessed the in vitro production of proinflammatory cytokines IL-6, IL-1beta, and TNF-alpha by peripheral blood mononuclear cells (PBMCs) in response to mitogen stimulation within a community-based sample of 79 midlife women. Results indicate that midlife women with higher levels of depressive symptoms (as assessed with the Center for Epidemiologic Studies Depression scale) and greater body mass index (BMI) displayed diminished production of IL-6, IL-1beta, and TNF-alpha by stimulated PBMCs, as compared with their less-depressed counterparts. These relationships remained after controlling for such health-related variables as age, recent sleep disruption, physical activity level, and self-reported medical history. In contrast, depressive symptoms were not significantly associated with circulating levels of the same proinflammatory cytokines (IL-6, IL-1beta, and TNF-alpha) obtained from serum samples available for a subset of 62 of the study participants. Moreover, circulating proinflammatory cytokine levels were not significantly associated with the in vitro proinflammatory cytokine production outcomes. Further research is needed to clarify the clinical significance of the current study findings, and the extent to which in vitro tests of stimulated proinflammatory cytokine production are associated with other measures of cellular immune function and/or circulating markers of systemic inflammation obtained across various study populations.Brain Behavior and Immunity 03/2007; 21(2):229-37. DOI:10.1016/j.bbi.2006.07.005 · 6.13 Impact Factor