title: Immune-mediated processes implicated in chemotherapy-induced peripheral neuropathy.
abstract: Chemotherapy-induced peripheral neuropathy (CIPN) and associated neuropathic pain are challenging complications of cancer treatment. Many of the major classes of chemotherapeutics can cause neurotoxicity and significantly modulate the immune system. There is ongoing investigation regarding whether reciprocal crosstalk between the nervous and immune systems occurs and, indeed, contributes to neuropathic pain during treatment with chemotherapeutics. An emerging concept is that neuroinflammation is one of the major mechanisms underlying CIPN. Here, we discuss recent findings, which provide insight into this complex process of neuroimmune interactions. Findings show limited infiltration of leukocytes into the nervous system of CIPN animals and varying degrees of peripheral and central glial activation depending on the chemotherapeutic drug, dose, schedule, and timing. Most evidence suggests an increase in pro-inflammatory cytokine expression and changes in immune signalling pathways. There is, however, limited evidence available from human studies and it remains unclear whether neuroinflammatory responses are the cause of neuropathy or a bystander effect of the chemotherapy treatment.
authors.affiliation: School of Medical Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia. Electronic address: justin.lees@unsw.edu.au.
authors.forename: Justin G
authors.initials: JG
authors.lastname: Lees
authors.affiliation: School of Medical Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Preet G S
authors.initials: PG
authors.lastname: Makker
authors.affiliation: School of Medical Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Tonkin
authors.affiliation: School of Medical Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Munawwar
authors.initials: M
authors.lastname: Abdulla
authors.affiliation: Brain and Mind Centre, University of Sydney, NSW, 2050, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Susanna B
authors.initials: SB
authors.lastname: Park
authors.affiliation: Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, 2052, Australia; Department of Medical Oncology, Prince of Wales Hospital, Sydney, 2031, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Goldstein
authors.affiliation: School of Medical Sciences, The University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Gila
authors.initials: G
authors.lastname: Moalem-Taylor
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D009437:Neuralgia / Q000139:chemically induced* / Q000276:immunology; D009457:Neuroglia / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D018925:Chemokines; D016207:Cytokines
keywords: Chemotherapy-induced peripheral neuropathy; Hypersensitivity; Immune cell activation; Neuroinflammation; Neurotoxicity; Paraesthesia