Targeting interleukin-20 alleviates paclitaxel-induced peripheral neuropathy

Li Hsien Chen, Yu Min Yeh, Yi Fan Chen, Yu Hsiang Hsu, Hsiao Hsuan Wang, Peng Chan Lin, Lian Yun Chang, Chou Ching K. Lin, Ming Shi Chang, Meng Ru Shen

研究成果: Article同行評審

11 引文 斯高帕斯(Scopus)

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 Ca 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 Ca homeostasis. Therefore, the anti-IL-20 monoclonal antibody is a promising therapeutic for the prevention and treatment of paclitaxel-induced neuropathy.

原文English
頁(從 - 到)1237-1254
頁數18
期刊Pain
161
發行號6
DOIs
出版狀態Published - 2020 6月 1

All Science Journal Classification (ASJC) codes

  • 神經內科
  • 神經病學(臨床)
  • 麻醉與疼痛醫學

指紋

深入研究「Targeting interleukin-20 alleviates paclitaxel-induced peripheral neuropathy」主題。共同形成了獨特的指紋。

引用此