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

• DOI: 10.1186/s12974-018-1270-x
• Publication Date: 2018-08-21T11:23:52Z
• Authors: Cristina Meregalli; Ivan Marjanovic; Carla Scali; Laura Monza; Nadia Spinoni; Cristina Galliani; Rinaldo Brivio; Alessia Chiorazzi; Elisa Ballarini; Virginia Rodrigue...; Valentina Alda Ca...; Paola Alberti; Giulia Fumagalli; Eleonora Pozzi; Annalisa Canta; Marina Quartu; Chiara Briani; Norberto Oggioni; Paola Marmiroli; Guido Cavaletti
• Keywords: Neurotoxicity

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a severe adverse effect in patients receiving antitumor agents, and no effective treatment available. Although the mechanisms responsible for development of CIPN are poorly understood, recent findings make neuroinflammation an attractive target to be investigated, particularly when neuropathic pain prominent feature such as after bortezomib administration. The aim our study was evaluate intravenous immunoglobulins (IVIg) delivery chronic CIPN. related neuro-immune aspects were investigated well-characterized rat model bortezomib-induced (BIPN).After determination suitable schedule based on preliminary pharmacokinetic pilot study, female Wistar rats treated with IVIg 1 g/kg every 2 weeks. started at beginning administration ("preventive" schedule), or once BIPN already ensued 4 weeks ("therapeutic" schedule). Neurophysiological behavioral studies performed assess extent painful induced by bortezomib, these functional assessments completed pathologic examination nerves intraepidermal nerve fiber quantification (IENF). role innate immune response immunochemistry characterization macrophage infiltration nerves.Both schedules able significantly reduce heat mechanical allodynia. changes not evidenced neurophysiological nerves, they effects paralleled animals preventive reduced axonopathy significant protection from loss IENF. Moreover, very reducing macrophages M1, pro-inflammatory phenotype.Our results suggest that might considered possible safe therapeutic option preventing M1 infiltration. However, since frequent also other types, it indicates need further investigation forms