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KMID : 1009020180160010103
Clinical Psychopharmacology and Neuroscience
2018 Volume.16 No. 1 p.103 ~ p.108
Depression and Mania Induce Pro-inflammatory Activation of Macrophages Following Application of Serum from Individuals with Bipolar Disorder
Ferrari Pamela

Parisi Mariana Migliorini
Colombo Rafael
Becker Matheus
Fries Gabriel
Ascoli Bruna Maria
Gea Luiza Paul
Kauer-Sant¡¯anna Marcia
Kapczinski Flavio
Klamt Fabio
Guma Fatima T.C.R.
Rosa Adriane Ribeiro
Barbe-Tuana Florencia M.
Abstract
Objective: Evidence 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.

Methods: Eighteen 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.

Results: Macrophages exposed to serum of manic and depressive BD patients displayed an increase of interleukin-1¥â (6.40¡¾3.47 and 9.04¡¾5.84 vs. 0.23¡¾0.11; p£¼0.05) and tumor necrosis factor-¥á (2.23¡¾0.91 and 2.03¡¾0.45 vs. 0.62¡¾0.24; 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¡¾0.20 vs. 1.86¡¾1.61; p=0.006) and CXCL10 expression (0.36¡¾0.15 and 0.86¡¾0.24 vs. 1.83¡¾0.88; p£¼0.000 and p=0.04) compared to the euthymia group.

Conclusion: Our 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.
KEYWORD
Bipolar disorder, Cytokines, Chemokines, Macrophages, Polarization, U-937
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