Targeting interleukin-20 alleviates paclitaxel-induced peripheral neuropathy

Area of Science:

• Neuroscience
• Immunology
• Oncology

Background:

• Chemotherapy-induced peripheral neuropathy (CIPN) is a significant dose-limiting toxicity.
• The precise role of immune mediators, like proinflammatory cytokines, in CIPN pathogenesis is not fully understood.

Purpose of the Study:

• To investigate the contribution of interleukin-20 (IL-20) to paclitaxel-induced peripheral neuropathy.
• To explore IL-20 as a potential therapeutic target for preventing CIPN.

Main Methods:

• Measured serum IL-20 levels in cancer patients undergoing chemotherapy.
• Utilized mouse models of paclitaxel-induced neuropathy.
• Employed IL-20 neutralizing antibodies and genetic deletion of IL-20 receptors.
• Assessed neuroinflammation, nerve damage, and calcium homeostasis.

Main Results:

• Elevated serum IL-20 levels correlated with increased CIPN risk in patients.
• Paclitaxel treatment increased IL-20 levels in mice, linked to neuropathy development.
• Blocking IL-20 prevented CIPN, reduced nerve damage, and suppressed inflammatory responses.
• IL-20 upregulation by paclitaxel was mediated by dysregulated calcium homeostasis.
• IL-20 inhibition did not compromise paclitaxel's anti-cancer efficacy.

Conclusions:

• Interleukin-20 plays a critical role in paclitaxel-induced peripheral neuropathy.
• Targeting IL-20 ameliorates CIPN by mitigating neuroinflammation and restoring calcium balance.
• Anti-IL-20 monoclonal antibodies represent a promising therapeutic strategy for CIPN prevention and treatment without affecting chemotherapy efficacy.