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


CONCLUSIONS
IL-6 at low doses (10 microg/kg) provided protection against the development of CIN without demonstrating interference with the anti tumoural activity of these anti-mitotic drugs.
Callizot
Noelle
N
Neurofit, rue Jean Sapidus, Parc d'Innovation, 67400, Illkirch, France. noelle.callizot@gmail.com
Andriambeloson
Emile
E
Glass
Jonathan
J
Revel
Michel
M
Ferro
Pamela
P
Cirillo
Rocco
R
Vitte
Pierre-Alain
PA
Dreano
Michel
M
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D001259:Ataxia / Q000139:chemically induced / Q000517:prevention & control; D002396:Catechols / Q000494:pharmacology / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity*; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009431:Neural Conduction / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D017239:Paclitaxel / Q000627:therapeutic use / Q000633:toxicity*; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014183:Transplantation, Heterologous; D014750:Vincristine / Q000627:therapeutic use / Q000633:toxicity*
D000970:Antineoplastic Agents; D002396:Catechols; D015850:Interleukin-6; D018696:Neuroprotective Agents; C018599:4-methylcatechol; D014750:Vincristine; D017239:Paclitaxel; D002945:Cisplatin