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

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1237-1254
Number of pages18
JournalPain
Volume161
Issue number6
DOIs
Publication statusPublished - 2020 Jun 1

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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