Depression and mania induce pro-inflammatory activation of macrophages following application of serum from individuals with bipolar disorder.
Pamela Ferrari 1, 2, Mariana Migliorini Parisi 4, 8, Rafael Colombo 1, 5, Matheus Becker 4, 6, Gabriel Fries 1, 2, Bruna Maria Ascoli 1, 2, Luiza Paul Géa 1, 7, Márcia Kauer-Sant’anna 1, 2, Flavio Kapczinski 1, 2, Fábio Klamt 4, 6, Fátima T. C. R. Guma 4, 8, Adriane Ribeiro Rosa 1, 2, 7*, Florencia María Barbé-Tuana 4, 8
1Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA), Brazil., 1Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre (HCPA), Brazil., 2Postgraduate Program: Psychiatry and Behavioral Science, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (RS), Brazil., 2Postgraduate Program: Psychiatry and Behavioral Science, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (RS), Brazil., 3Laboratory of Molecular Biology and Bioinformatics, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil., 3Laboratory of Molecular Biology and Bioinformatics, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil., 4Postgraduate Program: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (RS), Brazil., 4Postgraduate Program: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (RS), Brazil., 5Laboratory of Pharmacology and Physiology, Universidade de Caxias do Sul (UCS), Brazil., 5Laboratory of Pharmacology and Physiology, Universidade de Caxias do Sul (UCS), Brazil., 6Laboratory of Cellular Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (RS), Brazil., 6Laboratory of Cellular Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre (RS), Brazil., 7Department of Pharmacology and Postgraduate Program: Pharmacology and Therapeutics, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil., 7Department of Pharmacology and Postgraduate Program: Pharmacology and Therapeutics, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil., 8Laboratory of Biochemistry and Cellular Biology of Lipids, Department of Biochemistry, ICBS/UFRGS, Porto Alegre (RS), Brazil., 8Laboratory of Biochemistry and Cellular Biology of Lipids, Department of Biochemistry, ICBS/UFRGS, Porto Alegre (RS), Brazil.
Received: December 18, 2016; Revised: April 21, 2017; Accepted: April 28, 2017; Published online: April 28, 2017.
© The Korean College of Neuropsychopharmacology. All rights reserved.

Abstract
Objective: Evidence suggests that immune imbalance is involved with bipolar disorder; however, its precise mechanism is poorly understood. This study investigated whether biochemical changes in the serum from bipolar disorder patients could modulate the phenotype of cultured macrophages.
Methods: Eighteen subjects with bipolar disorder and five healthy individuals were included. The human monocyte cell line U-937 was activated with phorbol 12-myristate 13-acetate and polarization induced with media supplemented with 10% serum from each patient for 24 hours. Gene expression of selected M1 and M2 markers was assessed by quantitative polymerase chain reaction.
Results: Macrophages exposed to serum of manic and depressive bipolar disorder patients displayed increased IL-1β (6.40 ± 3.47 and 9.04 ± 5.84 versus 0.23 ± 0.11; p < 0.05) and TNF-α (2.23 ± 0.91 and 2.03 ± 0.45 versus 0.62 ± 0.24; p = 0.002 and p = 0.004, respectively) compared to euthymic group (no difference between euthymic and controls). In parallel, macrophages treated with serum of patients in acute episode displayed down-regulation of CXCL9 (0.29 ± 0.20 versus 1.86 ± 1.61; p = 0.006) and CXCL10 expression (0.36 ± 0.15 and 0.86 ± 0.24 versus 1.83 ± 0.88; p < 0.000 and p = 0.04) compared to euthymia group.
Conclusion: Our results are consistent with previous studies showing that changes in peripheral blood markers could modulate M1/M2 polarization in bipolar disorder. Evidence of macrophages as source of inflammatory cytokines might be helpful to unravel how the mononuclear phagocyte system is involved in the etiology of bipolar disorder.
Keywords: Bipolar disorder, chemokines, cytokines, macrophages` polarization, neuroinflammation


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