Otani Kohei, Kagi Tomohiro, Noguchi Takuya, Suzuki Sara, Hirata Yusuke, Matsuzawa Atsushi
Laboratory of Health Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Department of Medical Biochemistry, School of Pharmacy, Iwate Medical University, Yahaba, Japan.
J Antibiot (Tokyo). 2025 Jun 2. doi: 10.1038/s41429-025-00835-6.
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.
多粘菌素B（PMB）是一种对包括多重耐药铜绿假单胞菌（MDRP）在内的多重耐药细菌有效的多肽抗生素。然而，PMB经常引发严重的急性肾衰竭（ARF）。我们最近的研究表明，PMB诱导的ARF是由NOD样受体蛋白3（NLRP3）炎性小体激活介导的炎症反应触发的。在此，我们提供证据表明，柳氮磺胺吡啶（SSZ），一种临床上使用的改善病情抗风湿药（DMARD），可以在ARF小鼠模型中改善PMB诱导的ARF。如先前所示，由于SSZ强烈抑制PMB在巨噬细胞中诱导的NLRP3炎性小体激活，PMB诱导的ARF的改善似乎是由NLRP3炎性小体激活的抑制引起的。因此，如果SSZ能够在临床实践中得到有效利用，就有可能克服多肽抗生素引起的ARF。
