• Li-Hsien Chen, Yu-Min Yeh, Yi-Fan Chen, Yu-Hsiang Hsu, Hsiao-Hsuan Wang, Peng-Chan Lin, Lian-Yun Chang, Lin Chou-Ching K CK Departments of Neurology., Ming-Shi Chang, and Meng-Ru Shen.
• Department of Pharmacology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Taiwan.
• Pain. 2020 Jun 1; 161 (6): 1237-1254.

AbstractThe 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.

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