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Papers of the Week


Papers: 15 Feb 2020 - 21 Feb 2020


Animal Studies, Pharmacology/Drug Development


2020 Feb 11


Pain

Targeting interleukin-20 alleviates paclitaxel-induced peripheral neuropathy.

Authors

Chen L-H, Yeh Y-M, Chen Y-F, Hsu Y-H, Wang H-H, Lin P-C, Chang L-Y, Lin C-CK, Chang M-S, Shen M-R
Pain. 2020 Feb 11.
PMID: 32068666.

Abstract

The role of immune mediators, including pro-inflammatory 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 up-regulated IL-20 via 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.