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

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 mu g/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 mu g/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 mu g/kg) provided protection against the development of CIN without demonstrating interference with the anti tumoural activity of these anti-mitotic drugs.