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Neuroimmunological Manifestations of Chemotherapy Exposure: Implications for Mucositis, Glia and Cognition

Juliana Esma Bajic, Gordon Stanley Howarth, Ian Neville Johnston, Mark Rowland Hutchinson

Chemotherapy drugs reduce quality of life often causing acute and delayed central side-effects, termed chemotherapy-induced cognitive impairment (CICI). Another dose-limiting chemotherapy-induced side-effect is oral and intestinal mucositis which results in significant gastrointestinal (GIT) damage and intestinal inflammation. Recent interest has been paid to neurological complications arising in patients with gut disorders, yet little attention has been paid to the role GIT damage plays in CICI. Our current understanding of neuronal adaptations and behavioral consequences resulting from immune system dysregulation has paved the way for investigation into the neuroimmunological manifestations associated with chemotherapy. In a clinical setting cancer patients experience a cluster of symptoms, similar to that manifested in cytokine-induced sickness responses. Accordingly, it is suggested that peripheral inflammatory events, such as chemotherapy-induced mucositis, may indirectly cause glial dysregulation and potentiate cognitive changes in CICI. Perhaps it is time to examine the cancer experience in a multidisciplinary manner, in order to encapsulate the direct and indirect mechanisms underlying treatment-related side-effects. Specifically, understanding the neuroimmunological implications of chemotherapy-induced mucositis will provide further insight into the direct and indirect mechanisms underlying CICI pathogenesis.