Depression and Mania Induce Pro-inflammatory Activation of Macrophages Following Application of Serum from Individuals with Bipolar Disorder

Abstract

ObjectiveEvidence has suggested that immune imbalance is involved with bipolar disorder (BD); however, its precise mechanism is poorly understood. This study investigated whether biochemical changes in the serum from BD patients could modulate the phenotype of cultured macrophages.MethodsEighteen subjects with BD and five healthy individuals were included in this study. The human monocyte cell line U-937 was activated with phorbol 12-myristate 13-acetate (PMA) and polarization was induced with RPMI-1640 media supplemented with 10% serum from each patient for 24 hours. Gene expression of selected M1 and M2 markers was assessed by quantitative PCR.ResultsMacrophages exposed to serum of manic and depressive BD patients displayed an increase of interleukin-1β (6.40±3.47 and 9.04±5.84 vs. 0.23±0.11; p<0.05) and tumor necrosis factor-α (2.23±0.91 and 2.03±0.45 vs. 0.62±0.24; p=0.002 and p=0.004, respectively) compared to euthymic group (there was no difference between euthymic and controls). In parallel, U-937 macrophages treated with serum of patients in acute episode displayed a down-regulation of CXCL9 (0.29±0.20 vs. 1.86±1.61; p=0.006) and CXCL10 expression (0.36±0.15 and 0.86±0.24 vs. 1.83±0.88; p<0.000 and p=0.04) compared to the euthymia group.ConclusionOur results are consistent with previous studies showing that changes in peripheral blood markers could modulate M1/M2 polarization in BD. The evidence of macrophages as source of inflammatory cytokines might be helpful to unravel how the mononuclear phagocyte system is involved in the etiology of BD.

Attenuated inflammatory response of monocyte-derived macrophage from patients with BD: a preliminary report

“…In particular, the overexpression of monocyte activation genes was evident in 60–70% of cases, most in patients with mania, current depression or active psychosis. More recently, we investigated whether biochemical changes in the serum from BD patients during episodes could modulate the phenotype of the U-937 monocytic cell line (Ferrari et al 2018). Our observations showed a robust upregulation in the expression of interleukin (IL)-1β and TNF in the cells that were treated with serum from manic and depressive patients compared with those treated with serum from euthymic patients (Ferrari et al 2018).…”

Antidepressant-like Effects Induced by Chronic Blockade of the Purinergic 2X7 Receptor through Inhibition of Non-like Receptor Protein 1 Inflammasome in Chronic Unpredictable Mild Stress Model of Depression in Rats

“…Numerous studies have highlighted the association between depression and inflammation 6–9). Patients with MDD have been reported to have higher levels of serum proinflammatory cytokines and acute phase reactants 10).…”

Evaluation of Endothelial Dysfunction in Bipolar Affective Disorders: Serum Endocan and Urotensin-II Levels

“…Activation of microglia in the brain by inflammatory signals strengthens the inflammatory response through the release of oxygen and nitrogen species, chemokines and cytokines 5–9). The role of inflammation and the immune system in BAD has also been supported by a large number of studies 5–9,39,40). Immune dysregulation is associated with changes in monoamine glutamate signaling and affected neurotrophic neuroplastic support in BAD, and all these can explain the rich metabolic and vascular co-morbidity as well as the etiopathogenesis of the disease and contributing to the variation in its course 41,42)…”