Targeting interleukin-20 alleviates paclitaxel-induced peripheral neuropathy

被引:34
|
作者
Chen, Li-Hsien [1 ]
Yeh, Yu-Min [2 ,3 ]
Chen, Yi-Fan [4 ]
Hsu, Yu-Hsiang [2 ]
Wang, Hsiao-Hsuan [4 ]
Lin, Peng-Chan [3 ]
Chang, Lian-Yun [1 ]
Lin, Chou-Ching K. [5 ]
Chang, Ming-Shi [6 ]
Shen, Meng-Ru [1 ,7 ]
机构
[1] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Pharmacol, Tainan, Taiwan
[2] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Inst Clin Med, Tainan, Taiwan
[3] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Internal Med, Tainan, Taiwan
[4] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Inst Basic Med Sci, Tainan, Taiwan
[5] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Dept Neurol, Coll Med, Tainan, Taiwan
[6] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Dept Biochem & Mol Biol, Coll Med, Tainan, Taiwan
[7] Natl Cheng Kung Univ, Natl Cheng Kung Univ Hosp, Coll Med, Dept Obstet & Gynecol, Tainan, Taiwan
关键词
IL-20; Paclitaxel; Neuroprotection; Chemotherapy-induced neuropathy; ANTI-INTERLEUKIN-20; MONOCLONAL-ANTIBODY; NEUROPROTECTIVE DRUG; IL-20; CONTRIBUTES; CHANNELS; PAIN; NEUROTOXICITY; EXPRESSION; PSORIASIS; MODELS;
D O I
10.1097/j.pain.0000000000001831
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
The role of immune mediators, including proinflammatory cytokines in chemotherapy-induced peripheral neuropathy (CIPN), remains unclear. Here, we studied the contribution of interleukin-20 (IL-20) to the development of paclitaxel-induced peripheral neuropathy. Increased serum levels of IL-20 in cancer patients with chemotherapy were accompanied by increased CIPN risk. In mouse models, proinflammatory IL-20 levels in serum and dorsal root ganglia fluctuated with paclitaxel treatment. Blocking IL-20 with the neutralizing antibody or genetic deletion of its receptors prevented CIPN, alleviated peripheral nerve damage, and dampened inflammatory responses, including macrophage infiltration and cytokine release. Mechanistically, paclitaxel upregulated IL-20 through dysregulated Ca2+ homeostasis, which augmented chemotherapy-induced neurotoxicity. Importantly, IL-20 suppression did not alter paclitaxel efficacy on cancer treatment both in vitro and in vivo. Together, targeting IL-20 ameliorates paclitaxel-induced peripheral neuropathy by suppressing neuroinflammation and restoring Ca2+ homeostasis. Therefore, the anti-IL-20 monoclonal antibody is a promising therapeutic for the prevention and treatment of paclitaxel-induced neuropathy.
引用
收藏
页码:1237 / 1254
页数:18
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