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<p>This study explored the potential immunomodulatory role of methylphenidate (MPH), specifically focusing on its modulation of the inflammatory response and the phosphoinositide 3-kinase (PI3K) signaling pathway in J774.2 murine macrophages. Cells were treated with increasing concentrations of MPH (1, 5, and 10&#xa0;μg/mL) in the presence or absence of lipopolysaccharide (LPS). Cytokine concentrations (TNF-α, IL-6, IL-12p40, and GM-CSF) were quantified using ELISA, and intracellular activation of the PI3K signaling pathway was assessed via flow cytometry. It was demonstrated that MPH strongly suppressed the inflammatory cytokines TNF-α, IL-6, and IL-12p40 in a dose-dependent manner (<i>p</i> &lt; 0.001), with significant suppression of GM-CSF evident at higher doses. Furthermore, flow cytometric analysis revealed that PI3K signaling was modulated in the presence of LPS, indicating a complex regulatory mechanism. Collectively, these findings suggest that MPH holds therapeutic potential for neuroinflammatory disorders through the dual action of suppressing inflammatory cytokines and modulating PI3K signaling pathways.</p>

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Methylphenidate modulates the ınflammatory response and PI3K signaling in macrophages

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月22日

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  • Semanur Ercan,
  • Batuhan Yurtseven,
  • Ömer Mete Başkan,
  • Ece Aydın,
  • Melek Ebrar Emer,
  • Esra Aydemir,
  • Furkan Ayaz

摘要

This study explored the potential immunomodulatory role of methylphenidate (MPH), specifically focusing on its modulation of the inflammatory response and the phosphoinositide 3-kinase (PI3K) signaling pathway in J774.2 murine macrophages. Cells were treated with increasing concentrations of MPH (1, 5, and 10 μg/mL) in the presence or absence of lipopolysaccharide (LPS). Cytokine concentrations (TNF-α, IL-6, IL-12p40, and GM-CSF) were quantified using ELISA, and intracellular activation of the PI3K signaling pathway was assessed via flow cytometry. It was demonstrated that MPH strongly suppressed the inflammatory cytokines TNF-α, IL-6, and IL-12p40 in a dose-dependent manner (p < 0.001), with significant suppression of GM-CSF evident at higher doses. Furthermore, flow cytometric analysis revealed that PI3K signaling was modulated in the presence of LPS, indicating a complex regulatory mechanism. Collectively, these findings suggest that MPH holds therapeutic potential for neuroinflammatory disorders through the dual action of suppressing inflammatory cytokines and modulating PI3K signaling pathways.