Intravenous Immunoglobulin Suppresses Chemotherapy-Induced Peripheral Neurotoxicity Via Macrophage Modulation in Rats and Mice

Abstract

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a serious adverse effect that leads to treatment discontinuation by patients receiving anticancer therapy. Treatment discontinuation is a serious and life-threatening problem for patients with cancer; hence, there is a need for drugs that suppress the induction of CIPN by anticancer drugs. Here, using rat and mouse models, we showed that intravenous immunoglobulin (IVIg) can suppress CIPN induced by not only paclitaxel but also by doxorubicin. Furthermore, the suppressive effect of IVIg is eliminated when macrophages are depleted. Here, we proposed two novel independent mechanisms underlying the alleviation of CIPN by IVIg. First, IVIg suppresses CIPN in a macrophage-dependent manner. Second, IVIg combined with anticancer drugs can avoid restrictions on the use of anticancer drugs owing to CIPN induction. However, further research is necessary for the bench-to-bedside translation of these novel applications of IVIg. Our findings lay a strong foundation for research on IVIg therapeutics.