Treatment with anti-TNF alpha protects against the neuropathy induced by the proteasome inhibitor bortezomib in a mouse model
Alé, Albert (Universitat Autònoma de Barcelona. Institut de Neurociències)
Bruna, Jordi (Universitat Autònoma de Barcelona. Institut de Neurociències)
Morell, Marta (Universitat Autònoma de Barcelona. Institut de Neurociències)
van de Velde, Helgi (Janssen Research and Development)
Monbaliu, Johan (Janssen Research and Development)
Navarro, X. (Xavier) (Universitat Autònoma de Barcelona. Institut de Neurociències)
Udina i Bonet, Esther (Universitat Autònoma de Barcelona. Institut de Neurociències)

Data:	2014
Resum:	Bortezomib (BTZ), a proteasome inhibitor, is an effective anti-neoplastic drug used in the treatment of multiple myeloma and mantle cell lymphoma. However, it can induce a reversible peripheral neuropathy that may lead to treatment discontinuation. The mechanism through which BTZ exerts toxic effects in peripheral neurons is not clear. Release of proinflammatory cytokines after nerve damage can induce neurodegeneration, but the effects of BTZ on cytokine expression in neurons are unknown, although BTZ modulates the expression of cytokines, such as TNF-α and IL-6, in tumor cells. The aim of this study was to evaluate the expression and the role of these cytokines on the course of BTZ induced neuropathy in mice. IL-6, TNF-α, TGF-β1 and IL-1β were up-regulated in dorsal root ganglia but TNF-α and IL-6 increased faster and higher. Then, we studied the potential neuroprotective effect of selective antibodies anti-TNF-α and anti-IL-6 on the evolution of the neuropathy. Treatment with anti-TNF-α but not with anti-IL-6 significantly prevented the decrease of sensory nerve action potentials amplitude and the loss of myelinated and unmyelinated fibers. We conclude that monoclonal antibodies directed against TNF-α may be a suitable neuroprotective therapy against the neurotoxicity induced by BTZ. © 2013 Elsevier Inc.
Ajuts:	Instituto de Salud Carlos III PI1100464
Drets:	Tots els drets reservats.
Llengua:	Anglès
Document:	Article ; recerca ; Versió sotmesa a revisió
Matèria:	Bortezomib ; Chemotherapy-induced peripheral neuropathy ; Cytokines ; Mice ; Neuropathy ; Proteasome inhibitor
Publicat a:	Experimental Neurology, Vol. 253 (march 2014) , p. 165-173, ISSN 1090-2430

DOI: 10.1016/j.expneurol.2013.12.020

28 p, 10.5 MB

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