High concentrations of serum interleukin-6 and interleukin-8 in patients with bipolar disorder

Abstract

Immune system dysregulation plays a key role in the physiopathology of bipolar disorder (BD) and major depressive disorder (MDD). However, whether interleukins might be biomarkers to distinguish these 2 affective disorders is unclear. Here, we assessed the differences in serum levels of interleukin 6 (IL-6) and interleukin 8 (IL-8) as well as C-reactive protein (CRP) in patients with MDD and BD. In total, we enrolled 21 MDD patients, 26 BD patients, and 20 healthy controls. We collected a total of 35 samples from BD patients in 3 different phases, depression phase, manic phase, and remission stage, and 27 samples from MDD patients in acute and remission phases. Serum IL-6 and IL-8 levels were assessed with solid phase sandwich ELISA-based quantitative arrays, and CRP levels were determined with an automatic analyzer. Both serum IL-6 and IL-8 levels were elevated in BD patients but not MDD patients. Subgroup analysis indicated elevated serum IL-6 in both the depression and manic phases in BD patients. The serum CRP levels did not change in either BD or MDD patients. However, sex differences in CRP concentrations were observed in healthy controls. Furthermore, there were linear correlations between the CRP levels and Bech-Rafaelsen Mania Rating Scale (BRMS) scores in BD patients. IL-6 and IL-8 levels may serve as biomarkers to differentiate between MDD and BD patients, even when the clinical manifestations are atypical. IL-6 may be used for the differential diagnosis of MDD and depressive episodes in BD.

Inflammation is Correlated with Abnormal Functional Connectivity in Unmedicated Bipolar Depression: A Resting State FMRI Study

“…In this study, we found increased pro-in ammatory cytokine levels of IL-6 and IL-8 in BD group when compared to HC, which was consistent with previous studies [26,28,30,87,88]. Furthermore, we found elevated levels of IL-8 correlated with the reduction of FC in the right precentral gyrus within SMN in BD.…”

“…Pro-in ammatory cytokines have been shown to access the brain [20] and interact with neurocircuits to in uence the risk for depression [21] and are implicated in many neurobiological processes including neuromodulator effects, neurotransmitter-like effects, regulation of neurogenesis that potentially relevant to psychiatric disorders such as BD [22]. Previous studies examined the relationship between in ammation and BD focusing on abnormal peripheral pro-in ammatory cytokines levels, and found signi cantly elevated levels of interleukin 6 (IL-6) [23][24][25][26] and interleukin 8 (IL-8) [27][28][29] in BD. Higher baseline IL-6 and IL-8 levels associated with poorer antidepressant responses have been found in BD [30].…”

Prefrontal dopamine D1 receptor manipulation influences anxiety behavior and induces neuroinflammation within the hippocampus

“…BD patients exhibit a persistent and low-grade pro-in ammatory state. This pro-in ammatory state is even more intense during mood episodes, especially manic episodes, and less intense in depressive episodes (Brietzke et al 2009b;Lu et al 2019;Modabbernia et al 2013). These ndings are supported by phasic differences in the peripheral levels of cytokines in BD patients (Ortiz-Domínguez et al 2007).…”

“…Chronic in ammatory processes, however, can cause severe side effects in the brain. For example, a persistent and low-grade proin ammatory state is present in BD patients (Brietzke et al 2009b;Goldsmith et al 2016b;Lu et al 2019;Modabbernia et al 2013). This chronic low-grade in ammation is characteristic for affective disorders and anxiety-related disorders, such as generalized anxiety disorder and post-traumatic stress disorder, too (Goldsmith et al 2016b;Haroon et al 2012;Michopoulos et al 2017).…”

Hypothesis: bipolar disorder is an Epstein–Barr virus‐driven chronic autoimmune disease – implications for immunotherapy

“…It has been hypothesised that intrathecal IgG synthesis with oligoclonal bands is caused by clonal expansion of EBV‐infected autoreactive B cells in the CNS 4 . Increased serum/plasma interleukin‐6 levels in BD 7,17,18 provide further evidence for a role of the immune system in the pathogenesis of BD.…”