High-dose intravenous immunoglobulins reduce nerve macrophage infiltration and the severity of bortezomib-induced peripheral neurotoxicity in rats

Autor: Virginia Rodriguez-Menendez, Elisa Ballarini, Marina Quartu, Chiara Briani, Annalisa Canta, Guido Cavaletti, Norberto Oggioni, Valentina Alda Carozzi, Paola Marmiroli, G Fumagalli, Alessia Chiorazzi, C Scali, Nadia Spinoni, Cristina Galliani, Laura Monza, Cristina Meregalli, Eleonora Pozzi, Paola Alberti, I Marjanovic, Rinaldo Brivio
Přispěvatelé: Meregalli, C, Marjanovic, I, Scali, C, Monza, L, Spinoni, N, Galliani, C, Brivio, R, Chiorazzi, A, Ballarini, E, Rodriguez-Menendez, V, Carozzi, V, Alberti, P, Fumagalli, G, Pozzi, E, Canta, A, Quartu, M, Briani, C, Oggioni, N, Marmiroli, P, Cavaletti, G
Rok vydání: 2018
Předmět:
0301 basic medicine
Neurology
Hot Temperature
Human intravenous immunoglobulin (IVIG)
Neural Conduction
Pharmacology
lcsh:RC346-429
Bortezomib
0302 clinical medicine
Nerve Fibers
Neuroinflammation
hemic and lymphatic diseases
Medicine
Skin
General Neuroscience
Peripheral
Allodynia
Neutrophil Infiltration
Hyperalgesia
Sensory Thresholds
Neuropathic pain
Cytokines
Neurotoxicity Syndromes
medicine.symptom
medicine.drug
medicine.medical_specialty
Immunology
Immunoglobulins
Antineoplastic Agents
03 medical and health sciences
Cellular and Molecular Neuroscience
Peripheral neurotoxicity
Neuroscience (all)
Bortezomib
Peripheral neurotoxicity
Allodynia
Human intravenous immunoglobulin (IVIG)
Neuroinflammation
Physical Stimulation
Animals
Immunologic Factors
Peripheral Nerves
Adverse effect
lcsh:Neurology. Diseases of the nervous system
business.industry
Macrophages
Research
Body Weight
Neurotoxicity
medicine.disease
Rats
Disease Models
Animal
030104 developmental biology
business
030217 neurology & neurosurgery
Zdroj: Journal of Neuroinflammation
Journal of Neuroinflammation, Vol 15, Iss 1, Pp 1-12 (2018)
ISSN: 1742-2094
Popis: Background Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe adverse effect in patients receiving antitumor agents, and no effective treatment is available. Although the mechanisms responsible for the development of CIPN are poorly understood, recent findings make neuroinflammation an attractive target to be investigated, particularly when neuropathic pain is a prominent feature such as after bortezomib administration. The aim of our study was to evaluate the effect of intravenous immunoglobulins (IVIg) delivery in chronic CIPN. The related neuro-immune aspects were investigated in a well-characterized rat model of bortezomib-induced peripheral neurotoxicity (BIPN). Methods After determination of a suitable schedule based on a preliminary pharmacokinetic pilot study, female Wistar rats were treated with IVIg 1 g/kg every 2 weeks. IVIg treatment was started at the beginning of bortezomib administration (“preventive” schedule), or once BIPN was already ensued after 4 weeks of treatment (“therapeutic” schedule). Neurophysiological and behavioral studies were performed to assess the extent of painful peripheral neurotoxicity induced by bortezomib, and these functional assessments were completed by pathologic examination of peripheral nerves and intraepidermal nerve fiber quantification (IENF). The role of the innate immune response in BIPN was investigated by immunochemistry characterization of macrophage infiltration in peripheral nerves. Results Both schedules of IVIg administration were able to significantly reduce bortezomib-induced heat and mechanical allodynia. Although these changes were not evidenced at the neurophysiological examination of peripheral nerves, they behavioral effects were paralleled in the animals treated with the preventive schedule by reduced axonopathy in peripheral nerves and significant protection from loss of IENF. Moreover, IVIg administration was very effective in reducing infiltration in peripheral nerves of macrophages with the M1, pro-inflammatory phenotype. Conclusion Our results suggest a prominent role of neuroinflammation in BIPN and that IVIg might be considered as a possible safe and effective therapeutic option preventing M1 macrophage infiltration. However, since neuropathic pain is frequent also in other CIPN types, it also indicates the need for further investigation in other forms of CIPN.
Databáze: OpenAIRE
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