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Revisiting bupropion anti-inflammatory action: involvement of the TLR2/TLR4 and JAK2/STAT3

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Abstract

There are accumulating reports regarding poor response to common antidepressant therapy. Antidepressant resistance is often linked to inflammatory system activation and patients displaying inflammation prior to the treatment are less responsive to antidepressants. We hypothesized that the inefficacy of antidepressant therapy in some patients may be attributable to the drugs’ inflammatory mode of action, which has been overlooked because of their substantial therapeutic benefit. Bupropion is a commonly prescribed antidepressant that is often used to treat seasonal affective disorders as well. Nevertheless, research suggests that bupropion causes inflammation and worsens depressive symptoms. Therefore, we investigated the impact of bupropion on cytokines of innate and adaptive immunity, as well as immune signaling pathways. We treated lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs) with different doses of bupropion. Pro-/anti-inflammatory cytokines [tumor necrosis factor alpha (TNFα), interleukin-1β (IL-1β), IL-17, and IL-10] were assessed at both transcriptional and translational levels as well as the involvement of JAK2 /STAT3, TLR2, and TLR4 signaling in this process. Bupropion reduced IL-17A, TNFα, and IL-1β protein levels in the cultures. Nonetheless, bupropion increased IL-1β (P < 0.0001), TNFα (P < 0.0001), and IL-17A (P < 0.05) mRNA levels. Treatment enhanced both IL-10 concentration (P < 0.0001) and gene expression (P < 0.0001). TLR2 (P < 0.0001), TLR4 (P < 0.0001), JAK2 (P < 0.0001), and STAT3 (P < 0.0001) gene expression also rose in response to bupropion. The findings imply that bupropion, particularly 50 μM and 100 μM, has pro-inflammatory effects and should be co-administered with anti-inflammatory medications, at least in patients with inflammatory conditions.

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Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank all people in Shahid Sadoughi University of medical sciences who kindly helped us to perform this investigation.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pharmacology, School of Pharmacy, Shahid Sadoughi University of Medical Sciences and Health Services, Shohaday-e-Gomnam Blvd., Alem Sq., Yazd, Iran

    Alireza Karimollah & Taha Vahid

  2. Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Shohaday-e-Gomnam Blvd., Alem Sq., Yazd, Iran

    Anahid Hemmatpur

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  1. Alireza Karimollah
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  2. Anahid Hemmatpur
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Correspondence to Alireza Karimollah.

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It is important to note that the volunteers gave consent to take part in the study. Tests with the use of human samples have been approved by the ethical committee of Shahid Sadoughi University of Medical Sciences with ethical code: ir.ssu.medicine.rec.1395.337.

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Karimollah, A., Hemmatpur, A. & Vahid, T. Revisiting bupropion anti-inflammatory action: involvement of the TLR2/TLR4 and JAK2/STAT3. Inflammopharmacol 29, 1101–1109 (2021). https://doi.org/10.1007/s10787-021-00829-4

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