Clin Psychopharmacol Neurosci.  2018 Feb;16(1):103-108. 10.9758/cpn.2018.16.1.103.

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

Affiliations
  • 1Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. adrianerrosa@gmail.com
  • 2Postgraduate Program: Psychiatry and Behavioral Science, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
  • 3Laboratory of Molecular Biology and Bioinformatics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
  • 4Postgraduate Program: Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
  • 5Laboratory of Cellular Biochemistry, Department of Biochemistry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
  • 6Department of Pharmacology and Postgraduate Program: Pharmacology and Therapeutics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
  • 7Laboratory of Pharmacology and Physiology, Universidade de Caxias do Sul, Petrópolis, Brazil.
  • 8Laboratory of Biochemistry and Cellular Biology of Lipids, Department of Biochemistry, ICBS/UFRGS, Porto Alegre, Brazil.

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-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.
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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