Journal Article

Interleukin-6 protects against paclitaxel, cisplatin and vincristine-induced neuropathies without impairing chemotherapeutic activity

Revel, Michel, Callizot, Noelle, Dreano, Michel, Ferro, Pamela, Cirillo, Rocco, Vitte, Pierre-Alain, Andriambeloson, Emile, Glass, Jonathan

2008

Overview

Purpose This study was conducted to investigate the potential neuroprotective effect of IL-6 on chemotherapy induced neuropathy (CIN). IL-6 was compared to four-methylcatechol (4-MC)-a known inducer of NGF secretion previously shown to exhibit neuroprotective effects in CIN models. Methods Three CIN models were used; two in rats (cisplatin and vincristine) and one in mice (paclitaxel). IL-6 was delivered in four different doses in rats (0.3, 1, 3, 10 μg/kg, sc) every day from the first day of chemotherapeutic agent intoxication until the end of the study (day 37 for cisplatin protocol and day 30 for vincristine procedure). In mice, IL-6 was delivered at 10 μg/kg, sc either daily or three times a week from the first day of intoxication until the end of the study (day 19). Behavioral testings (hot plate and rotarod), nerve conduction studies (CMAP, SNCV, H-wave) and histo-morphometric analysis were done for all models. In addition, we tested whether IL-6 interfered with the tumor-reducing effects of the chemotherapeutic agents. Results IL-6 treatment prevented the behavioral and electrophysiological abnormalities produced by vincristine, cisplatin and Taxol intoxication, and similarly prevented the pathological changes in peripheral nerves. The neuroprotective action of chronic IL-6 treatment was at least equal to that of 4-MC. In addition, IL-6 neither inhibited the antitumour activity of cisplatin, nor stimulated tumour growth. Conclusion IL-6 at low doses (10 μg/kg) provided protection against the development of CIN without demonstrating interference with the anti tumoural activity of these anti-mitotic drugs.

• Publisher: Springer-Verlag,Springer,Springer Nature B.V
• Subject: Adenocarcinoma - drug therapy / Adenocarcinoma - pathology / Aged / Animals / Antineoplastic agents / Antineoplastic Agents - therapeutic use / Antineoplastic Agents - toxicity / Ataxia - chemically induced / Ataxia - prevention & control / Biological and medical sciences / Cancer Research / Catechols - pharmacology / Catechols - therapeutic use / Cisplatin - therapeutic use / Cisplatin - toxicity / Colonic Neoplasms - drug therapy / Colonic Neoplasms - pathology / Drug Evaluation, Preclinical / Female / Humans / Interleukin-6 - administration & dosage / Interleukin-6 - pharmacology / Interleukin-6 - therapeutic use / Medical sciences / Medicine / Medicine & Public Health / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Neural Conduction - drug effects / Neuroprotective Agents - administration & dosage / Neuroprotective Agents - pharmacology / Neuroprotective Agents - therapeutic use / Oncology / Original Article / Paclitaxel - therapeutic use / Paclitaxel - toxicity / Pain Threshold - drug effects / Peripheral Nervous System Diseases - chemically induced / Peripheral Nervous System Diseases - prevention & control / Pharmacology. Drug treatments / Pharmacology/Toxicology / Postural Balance - drug effects / Rats / Rats, Inbred Strains / Transplantation, Heterologous / Vincristine - therapeutic use / Vincristine - toxicity