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<p>Polymyxin B (PMB) is a polypeptide antibiotic active against multidrug-resistant bacteria, including multidrug-resistant <i>Pseudomonas aeruginosa</i> (MDRP). However, PMB frequently initiates serious acute renal failure (ARF). Our recent study demonstrated that PMB-induced ARF is triggered by inflammatory responses mediated by activation of the NOD-like receptors protein 3 (NLRP3) inflammasome. Here, we provide evidence that sulfasalazine (SSZ), a clinically-used disease-modifying antirheumatic drug (DMARD), can ameliorate PMB-induced ARF in a mouse model of ARF. Since SSZ strongly inhibited the NLRP3 inflammasome activation induced by PMB in macrophages, as previously demonstrated, the amelioration of PMB-induced ARF appears to be brought about by the inhibition of the NLRP3 inflammasome activation. Thus, if SSZ could be effectively utilized in clinical practice, it may be possible to overcome ARF caused by polypeptide antibiotics.</p>

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The antirheumatic drug sulfasalazine ameliorates acute renal failure (ARF) induced by polymyxin B

  • 期刊论文

  • 发表日期：

    2025年6月2日

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  • Kohei Otani,
  • Tomohiro Kagi,
  • Takuya Noguchi,
  • Sara Suzuki,
  • Yusuke Hirata,
  • Atsushi Matsuzawa

摘要

Polymyxin B (PMB) is a polypeptide antibiotic active against multidrug-resistant bacteria, including multidrug-resistant Pseudomonas aeruginosa (MDRP). However, PMB frequently initiates serious acute renal failure (ARF). Our recent study demonstrated that PMB-induced ARF is triggered by inflammatory responses mediated by activation of the NOD-like receptors protein 3 (NLRP3) inflammasome. Here, we provide evidence that sulfasalazine (SSZ), a clinically-used disease-modifying antirheumatic drug (DMARD), can ameliorate PMB-induced ARF in a mouse model of ARF. Since SSZ strongly inhibited the NLRP3 inflammasome activation induced by PMB in macrophages, as previously demonstrated, the amelioration of PMB-induced ARF appears to be brought about by the inhibition of the NLRP3 inflammasome activation. Thus, if SSZ could be effectively utilized in clinical practice, it may be possible to overcome ARF caused by polypeptide antibiotics.