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<p>Major Depressive Disorder (MDD) is increasingly recognized as a neuroinflammatory condition characterized by dysregulated cytokine networks. This comprehensive review examines the immunomodulatory effects of antidepressant medications, revealing their significant impact on Th1/Th2 cytokine balance beyond their classical neurotransmitter actions. Clinical data show that diverse antidepressant classes consistently demonstrate immunomodulatory properties that extend beyond their classical neurotransmitter effects. These medications reduce pro-inflammatory markers (IFN-γ, TNF-α, IL-6) while enhancing anti-inflammatory cytokines (IL-10, TGF-β), effects particularly relevant for treatment-resistant cases with elevated baseline inflammation. The therapeutic potential of these immunoregulatory effects is supported by emerging interventions, including low-dose IL-2 immunotherapy, vagus nerve stimulation, and microbiota-targeted therapies, which show promise for specific depression subtypes. Importantly, these approaches appear most effective when guided by inflammatory biomarkers, suggesting a path toward personalized treatment strategies. By integrating findings from clinical studies and translational research, this work establishes immune modulation as a fundamental component of antidepressant action. The review provides a framework for developing next-generation treatments that target neuroimmune pathways in MDD, with particular emphasis on practical applications for treatment-resistant cases. These insights bridge the gap between neuropharmacology and clinical psychiatry, offering new therapeutic possibilities for patients with inflammation-associated depression.</p>

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Modulation of neuroimmune cytokine networks by antidepressants: implications in mood regulation

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月23日

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  • Roseane Galdioli Nava,
  • Anny Silva Adri,
  • Igor Salerno Filgueiras,
  • Adriel Leal Nóbile,
  • Pedro Marçal Barcelos,
  • Yohan Lucas Gonçalves Corrêa,
  • Sergio Felipe de Oliveira,
  • Gustavo Cabral-Miranda,
  • Haroldo Dutra Dias,
  • Lena F. Schimke,
  • René de Araújo Gleizer,
  • Rodrigo Juliani Siqueira Dalmolin,
  • Helder I. Nakaya,
  • Rafael Machado Rezende,
  • Otavio Cabral-Marques

摘要

Major Depressive Disorder (MDD) is increasingly recognized as a neuroinflammatory condition characterized by dysregulated cytokine networks. This comprehensive review examines the immunomodulatory effects of antidepressant medications, revealing their significant impact on Th1/Th2 cytokine balance beyond their classical neurotransmitter actions. Clinical data show that diverse antidepressant classes consistently demonstrate immunomodulatory properties that extend beyond their classical neurotransmitter effects. These medications reduce pro-inflammatory markers (IFN-γ, TNF-α, IL-6) while enhancing anti-inflammatory cytokines (IL-10, TGF-β), effects particularly relevant for treatment-resistant cases with elevated baseline inflammation. The therapeutic potential of these immunoregulatory effects is supported by emerging interventions, including low-dose IL-2 immunotherapy, vagus nerve stimulation, and microbiota-targeted therapies, which show promise for specific depression subtypes. Importantly, these approaches appear most effective when guided by inflammatory biomarkers, suggesting a path toward personalized treatment strategies. By integrating findings from clinical studies and translational research, this work establishes immune modulation as a fundamental component of antidepressant action. The review provides a framework for developing next-generation treatments that target neuroimmune pathways in MDD, with particular emphasis on practical applications for treatment-resistant cases. These insights bridge the gap between neuropharmacology and clinical psychiatry, offering new therapeutic possibilities for patients with inflammation-associated depression.