Increase in Interleukin-6 Levels Is Related to Depressive Phenomena in the Acute (Relapsing) Phase of Multiple Sclerosis

Koutsouraki, Euphrosyni; Hatzifilipou, Eleni; Michmizos, Dimitrios; Cotsavasiloglou, C.; Costa, Vassiliki; Baloyannis, Stavros J.

doi:10.1176/jnp.23.4.jnp442

Cited by 16 publications

(8 citation statements)

References 29 publications

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“…Increased IL-6 and lowered albumin are well-established inflammatory markers of depression [45][46][47][48]. Our data that IL-6 levels are increased in patients with MS and depression extend those of Koutsouraki et al [49] showing that increased serum IL-6 levels were found in acute phase MS patients with depression versus those without depression. Thus, not only depression in the remission phase (our study) but also depression in the acute state of MS is accompanied by increased IL-6 levels.…”

Section: Discussionsupporting

confidence: 88%

“…Thus, our results do not allow to conclude whether the increased IL-6 levels in MS with depression indicate increased anti-inflammatory or proinflammatory effects. Interestingly, Koutsouraki et al [49] found that serum IL-6 and sIL-6R levels were significantly higher in acute phase MS patients with depression than in the remission group.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it may be that a condition characterized by chronic low-grade inflammation, subtle increases in BBB permeability, degeneration, and repair, is more likely to be accompanied by elevated depressive symptoms than the acute inflammatory state. Nevertheless, as described in the BIntroduction,^during acute MS attacks, the increased production of IL-6, TNF-α, and IFN-γ is significantly associated with increased depression or severity of depression [32,49]. Thus, it appears that depressive symptoms are related to cytokine production and immune-inflammatory markers not only during the acute phase of illness but also during the progressive course of illness, characterized by systemic inflammation, as shown in the present study, macrophage infiltration around the plaques, degenerative processes, and tissue repair.…”

Section: Discussionmentioning

confidence: 99%

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Immune-Inflammatory and Oxidative and Nitrosative Stress Biomarkers of Depression Symptoms in Subjects with Multiple Sclerosis: Increased Peripheral Inflammation but Less Acute Neuroinflammation

et al. 2015

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There is evidence that activated immune-inflammatory and oxidative and nitrosative stress (IO&NS) pathways play a role in the pathophysiology of multiple sclerosis (MS) and depression. This study examines serum levels of interleukin (IL)-1β, IL-4, IL-6, and IL-10; peroxides (LOOH); nitric oxide metabolites (NOx); albumin; ferritin; C-reactive protein (CRP); and tumor necrosis factor (TNF)-β NcoI polymorphism (rs909253) and gadolinium-enhanced magnetic resonance imaging (MRI) scan in MS patients with (n = 42) and without (n = 108) depression and normal controls (n = 249). Depression is scored using the depressive subscale of the Hospital Anxiety and Depression Scale (HADS). The extent of neurological disability is measured using the Expanded Disability Status Scale (EDSS) at the same time of the abovementioned measurements and 5 years earlier. Disease progression is assessed as actual EDSS-EDSS 5 years earlier. Three variables discriminate MS patients with depression from those without depression, i.e., increased IL-6 and lower IL-4 and albumin. Binary logistic regression showed that MS with depression (versus no depression) was characterized by more gastrointestinal symptoms and disease progression, higher serum IL-6, and lower albumin levels. In subjects with MS, the HADS score was significantly predicted by three EDSS symptoms, i.e., pyramidal, gastrointestinal, and visual symptoms. Fifty-eight percent of the variance in the HADS score was predicted by gastrointestinal symptoms, visual symptoms, the TNFB1/B2 genotype, and contrast enhancement (both inversely associated). There were no significant associations between depression in MS and type of MS, duration of illness, age, sex, nicotine dependence, and body mass index. MS with depression is associated with signs of peripheral inflammation, more disability, disease progression, gastrointestinal and visual symptoms, but less contrast enhancement as compared to MS without depression. It is concluded that depression is part of the neurological symptoms of MS and that its expression is primed by peripheral inflammation while acute neuroinflammation and the TNFB1/B2 genotype may be protective.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Immune-Inflammatory and Oxidative and Nitrosative Stress Biomarkers of Depression Symptoms in Subjects with Multiple Sclerosis: Increased Peripheral Inflammation but Less Acute Neuroinflammation

et al. 2015

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“…They investigated therapeutic effects related to cytokines, MBP-specific antibodies, and regulatory T-cell by analysis after irradiation. Previous studies have shown an increase in IL-6 levels in the serum of MS patients (Stelmasiak et al 2001;Koutsouraki et al 2011;Chen et al 2012). IL-6 has been implicated in neuroinflammatory reactions and is involved in multiple physiological central nervous system (CNS) processes such as neuron homeostasis, astrogliogenesis, and neuronal differentiation (Spooren et al 2011).…”

Section: Multiple Sclerosis (Ms)mentioning

confidence: 90%

Effects of Low-Dose-Gamma Rays on the Immune System of Different Animal Models of Disease

Shimura

Kojima

2014

Dose-Response

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ᮀ We reviewed the beneficial or harmful effects of low-dose ionizing radiation on several diseases based on a search of the literature. The attenuation of autoimmune manifestations in animal disease models irradiated with low-dose γ-rays was previously reported by several research groups, whereas the exacerbation of allergic manifestations was described by others. Based on a detailed examination of the literature, we divided animal disease models into two groups: one group consisting of collagen-induced arthritis (CIA), experimental encephalomyelitis (EAE), and systemic lupus erythematosus, the pathologies of which were attenuated by low-dose irradiation, and another group consisting of atopic dermatitis, asthma, and Hashimoto's thyroiditis, the pathologies of which were exacerbated by low-dose irradiation. The same biological indicators, such as cytokine levels and Tcell subpopulations, were examined in these studies. Low-dose irradiation reduced interferon (IFN)-gamma (γ) and interleukin (IL)-6 levels and increased IL-5 levels and the percentage of CD4Treg cells in almost all immunological disease cases examined. Variations in these biological indicators were attributed to the attenuation or exacerbation of the disease's manifestation. We concluded that autoimmune diseases caused by autoantibodies were attenuated by low-dose irradiation, whereas diseases caused by antibodies against external antigens, such as atopic dermatitis, were exacerbated.

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“…However, previous studies have reached divergent conclusions about the relationship between depression and the levels of IL-6. Increased IL-6 levels have been observed during depression [4,23-28]. However, psychological symptoms, such as a negative mood, tension, and fatigue, are significantly associated with a greater nocturnal decrease of IL-6 levels [29].…”

Section: Introductionmentioning

confidence: 99%

The effect of sunlight exposure on interleukin-6 levels in depressive and non-depressive subjects

et al. 2013

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BackgroundThe objective of this epidemiological study was to evaluate the effect of length of sunlight exposure on interleukin 6 (IL-6) levels in depressive and non-depressive subjects.MethodsThis was a cross-sectional study with 154 subjects (54 males, mean age: 43.5 ± 12.8 years) who were living in a rural area in south Brazil. Chronobiological and light parameters were assessed using the Munich Chronotype Questionnaire. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index. Depressive symptoms were assessed with the Beck Depression Inventory. Plasma levels of inflammatory cytokines (IL-2, IL-4, IL-6, IL-10, tumor necrosis factor-α, and interferon) were collected during the daytime and measured.ResultsIL-6 levels showed a positive correlation with light exposure (r = 0.257; p < 0.001) and a negative correlation with the mid-sleep phase on work-free days (r = -0.177; p = 0.028). Multiple linear regression analysis showed that only the length of light exposure was an independent factor for predicting IL-6 levels (ß = 0.26; p = 0.002). In non-depressed subjects, exposure to a different intensity of light did not affect IL-6 levels (t = -1.6; p = 0.1). However, when the two depressive groups with low and high light exposure were compared, the low light exposure group had lower levels of IL-6 compared with the high light exposure group (t = -2.19 and p = 0.0037).ConclusionsThe amount of time that participants are exposed to sunlight is directly related to their IL-6 levels. Additionally, depressed subjects differ in their IL-6 levels if they are exposed to light for differing amounts of time.

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Increase in Interleukin-6 Levels Is Related to Depressive Phenomena in the Acute (Relapsing) Phase of Multiple Sclerosis

Cited by 16 publications

References 29 publications

Immune-Inflammatory and Oxidative and Nitrosative Stress Biomarkers of Depression Symptoms in Subjects with Multiple Sclerosis: Increased Peripheral Inflammation but Less Acute Neuroinflammation

Immune-Inflammatory and Oxidative and Nitrosative Stress Biomarkers of Depression Symptoms in Subjects with Multiple Sclerosis: Increased Peripheral Inflammation but Less Acute Neuroinflammation

Effects of Low-Dose-Gamma Rays on the Immune System of Different Animal Models of Disease

The effect of sunlight exposure on interleukin-6 levels in depressive and non-depressive subjects

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