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Background <p>Macrophages are essential immune cells during <i>Leishmania</i> infection, as their polarization toward M1/M2 phenotypes determines disease outcome. This study aimed to investigate the modulatory effects of leptin, alone and in combination with glucantime, on macrophage polarization in <i>Leishmania tropica</i> infection.</p> Methods <p>Human THP-1-derived macrophages infected with <i>L. tropica</i> were treated with leptin (5 or 10&#xa0;ng/ml), glucantime (100 or 200&#xa0;μg/ml), or their combinations. The cytotoxic effects, parasite survival, reactive oxygen species (ROS), nitric oxide (NO) generation, and expression of M1/M2 acrophage-related parameters were evaluated using standard methods.</p> Results <p>Both leptin doses significantly increased the expression of M1-associated markers (CD86, iNOS, SOCS3, miR-155) and pro-inflammatory cytokines (TNF-α, IL-12, IFN-γ) while decreasing M2-associated markers (CD206, ARG1, SOCS1, miR-146a) and anti-inflammatory cytokines (IL-4, IL-10, TGF-β). The leptin-glucantime combinations showed synergistic effects, shifting macrophage polarization toward the M1 phenotype more than either treatment alone. In particular, the combination of 10&#xa0;ng/ml leptin with 100&#xa0;μg/ml glucantime completely eliminated intracellular amastigotes and showed a superior selectivity index (17.66) compared to mono-treatment (leptin: 7.88; glucantime: 6.87).</p> Conclusions <p>The findings indicate that leptin enhances the efficacy of glucantime against <i>L. tropica</i> by promoting M1 macrophage polarization. This presents a potential therapeutic approach that may lower conventional drug doses and associated toxicity while preserving or even improving treatment outcomes.</p> Graphical Abstract <p></p>

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Leptin enhances the efficacy of glucantime to modulate macrophage polarization toward the M1 phenotype in Leishmania tropica-infected macrophages

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月25日

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  • Alireza Keyhani,
  • Abdollah Jafarzadeh,
  • Iraj Sharifi,
  • Ehsan Salarkia

摘要

Background

Macrophages are essential immune cells during Leishmania infection, as their polarization toward M1/M2 phenotypes determines disease outcome. This study aimed to investigate the modulatory effects of leptin, alone and in combination with glucantime, on macrophage polarization in Leishmania tropica infection.

Methods

Human THP-1-derived macrophages infected with L. tropica were treated with leptin (5 or 10 ng/ml), glucantime (100 or 200 μg/ml), or their combinations. The cytotoxic effects, parasite survival, reactive oxygen species (ROS), nitric oxide (NO) generation, and expression of M1/M2 acrophage-related parameters were evaluated using standard methods.

Results

Both leptin doses significantly increased the expression of M1-associated markers (CD86, iNOS, SOCS3, miR-155) and pro-inflammatory cytokines (TNF-α, IL-12, IFN-γ) while decreasing M2-associated markers (CD206, ARG1, SOCS1, miR-146a) and anti-inflammatory cytokines (IL-4, IL-10, TGF-β). The leptin-glucantime combinations showed synergistic effects, shifting macrophage polarization toward the M1 phenotype more than either treatment alone. In particular, the combination of 10 ng/ml leptin with 100 μg/ml glucantime completely eliminated intracellular amastigotes and showed a superior selectivity index (17.66) compared to mono-treatment (leptin: 7.88; glucantime: 6.87).

Conclusions

The findings indicate that leptin enhances the efficacy of glucantime against L. tropica by promoting M1 macrophage polarization. This presents a potential therapeutic approach that may lower conventional drug doses and associated toxicity while preserving or even improving treatment outcomes.

Graphical Abstract