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Article

Human Intravenous Immunoglobulin Alleviates Neuropathic Symptoms in a Rat Model of Paclitaxel-Induced Peripheral Neurotoxicity

1
Experimental Neurology Unit, School of Medicine and Surgery, and NeuroMI (Milan Center for Neuroscience), University of Milano-Bicocca, 20900 Monza, Italy
2
Global Medical and R&D Department, Kedrion S.p.A., Località Ai Conti, Castelvecchio Pascoli, 55051 Lucca, Italy
3
Department of Biotechnology and Biosciences, University of Milano-Bicocca, 20126 Milan, Italy
*
Author to whom correspondence should be addressed.
Cristina Meregalli and Laura Monza equally contributed to this work.
Academic Editor: Andreas Spittler
Int. J. Mol. Sci. 2021, 22(3), 1058; https://doi.org/10.3390/ijms22031058
Received: 29 December 2020 / Revised: 17 January 2021 / Accepted: 18 January 2021 / Published: 21 January 2021
(This article belongs to the Special Issue Immunoglobulins in Inflammation)
The onset of chemotherapy-induced peripheral neurotoxicity (CIPN) is a leading cause of the dose reduction or discontinuation of cancer treatment due to sensory symptoms. Paclitaxel (PTX) can cause painful peripheral neuropathy, with a negative impact on cancer survivors’ quality of life. While recent studies have shown that neuroinflammation is involved in PTX-induced peripheral neurotoxicity (PIPN), the pathophysiology of this disabling side effect remains largely unclear and no effective therapies are available. Therefore, here we investigated the effects of human intravenous immunoglobulin (IVIg) on a PIPN rat model. PTX-treated rats showed mechanical allodynia and neurophysiological alterations consistent with a severe sensory axonal polyneuropathy. In addition, morphological evaluation showed a reduction of intra-epidermal nerve fiber (IENF) density and evidenced axonopathy with macrophage infiltration, which was more prominent in the distal segment of caudal nerves. Three weeks after the last PTX injection, mechanical allodynia was still present in PTX-treated rats, while the full recovery in the group of animals co-treated with IVIg was observed. At the pathological level, this behavioral result was paralleled by prevention of the reduction in IENF density induced by PTX in IVIg co-treated rats. These results suggest that the immunomodulating effect of IVIg co-treatment can alleviate PIPN neurotoxic manifestations, probably through a partial reduction of neuroinflammation. View Full-Text
Keywords: paclitaxel; neuropathic pain; intravenous immunoglobulin (IVIg); chemotherapy; axon degeneration; IENF paclitaxel; neuropathic pain; intravenous immunoglobulin (IVIg); chemotherapy; axon degeneration; IENF
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MDPI and ACS Style

Meregalli, C.; Monza, L.; Chiorazzi, A.; Scali, C.; Guarnieri, C.; Fumagalli, G.; Alberti, P.; Pozzi, E.; Canta, A.; Ballarini, E.; Rodriguez-Menendez, V.; Oggioni, N.; Cavaletti, G.; Marmiroli, P. Human Intravenous Immunoglobulin Alleviates Neuropathic Symptoms in a Rat Model of Paclitaxel-Induced Peripheral Neurotoxicity. Int. J. Mol. Sci. 2021, 22, 1058. https://doi.org/10.3390/ijms22031058

AMA Style

Meregalli C, Monza L, Chiorazzi A, Scali C, Guarnieri C, Fumagalli G, Alberti P, Pozzi E, Canta A, Ballarini E, Rodriguez-Menendez V, Oggioni N, Cavaletti G, Marmiroli P. Human Intravenous Immunoglobulin Alleviates Neuropathic Symptoms in a Rat Model of Paclitaxel-Induced Peripheral Neurotoxicity. International Journal of Molecular Sciences. 2021; 22(3):1058. https://doi.org/10.3390/ijms22031058

Chicago/Turabian Style

Meregalli, Cristina, Laura Monza, Alessia Chiorazzi, Carla Scali, Chiara Guarnieri, Giulia Fumagalli, Paola Alberti, Eleonora Pozzi, Annalisa Canta, Elisa Ballarini, Virginia Rodriguez-Menendez, Norberto Oggioni, Guido Cavaletti, and Paola Marmiroli. 2021. "Human Intravenous Immunoglobulin Alleviates Neuropathic Symptoms in a Rat Model of Paclitaxel-Induced Peripheral Neurotoxicity" International Journal of Molecular Sciences 22, no. 3: 1058. https://doi.org/10.3390/ijms22031058

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