Interleukin-6 signaling pathway involved in major depressive disorder: selective serotonin reuptake inhibitor regulates IL-6 pathway

Marziye Askari 1 , Leila Jahangard 2 , Alireza Zamani 1 , Mohammad Haghighi 2 , Iraj Salehi 3 , Zohre Zareighane 1 , Ghasem Solgi 1 , Reza Shahbazi 2  and Mahdi Alahgholi-Hajibehzadhttp://orcid.org/https://orcid.org/0000-0002-8940-3847 1
  • 1 Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
  • 2 Research Center for Behavioral Disorders and Substances Abuse, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
  • 3 Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
Marziye Askari
  • Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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, Leila Jahangard
  • Research Center for Behavioral Disorders and Substances Abuse, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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, Alireza Zamani
  • Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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, Mohammad Haghighi
  • Research Center for Behavioral Disorders and Substances Abuse, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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, Iraj Salehi
  • Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
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, Zohre Zareighane
  • Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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, Ghasem Solgi
  • Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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, Reza Shahbazi
  • Research Center for Behavioral Disorders and Substances Abuse, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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and Mahdi Alahgholi-HajibehzadORCID iD: https://orcid.org/0000-0002-8940-3847

Abstract

Background

Evidence indicates that pro-inflammatory Th17 and Th1 cells are involved in major depressive disorder (MDD) pathogenesis. Development of Th17 and Th1 are regulated by IL-6 and IFN-γ, respectively. In this study, the levels of IL-6 and IFN-γ, and mRNA expression of related signaling components and, Th17/Th1 transcription factors were investigated in MDD patients with/without selective serotonin reuptake inhibitor (SSRI) medication.

Materials and methods

Forty-six patients and 38 healthy controls (HCs) were recruited. Twenty patients were received the SSRI (sertraline 50–200 mg/day) for at least 1 year, and 26 patients were not received medication. Expression of IL-6R, IFN-γR, JAK1, JAK2, TYK2, STAT1, STAT3, T-bet and RORγt were assessed with Real-Time-PCR. Serum and supernatant levels of IL-6 and IFN-γ were determined using ELISA.

Results and discussion

The serum and supernatant levels of IL-6 were increased in patients without (SSRI) compared with HCs, while its levels was reduced in SSRI+. Elevated expressions of IL-6R, STAT3 and RORγt were observed in SSRI compared with HCs. Expressions of IL-6R, STAT3, RORγt and IFN-γR, were decreased in SSRI+ compared to SSRI patients.

Conclusion

Increased IL-6 involved in MDD, and SSRI regulates IL-6 pathway and IL-6 production. MDD patients may benefit from IL-6/IL-6R targeted therapeutic intervention.

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Turkish Journal of Biochemistry (TJB), official journal of Turkish Biochemical Society, is issued electronically every 2 months. The main aim of the journal is to support the research and publishing culture by ensuring that every published manuscript has an added value and thus providing international acceptance of the “readability” of the manuscripts published in the journal.

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