Interleukin-4 protects from chemotherapy-induced peripheral neuropathy in mice modal via the stimulation of IL-4/STAT6 signaling

Shi, Qingbin; Cai, Xiuying; Shi, Guixiang; Lv, Xingle; Yu, Jinping; Wang, Rui

doi:10.1590/s0102-865020180060000003

Cited by 15 publications

(10 citation statements)

References 27 publications

(26 reference statements)

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“…All these changes were reduced by administration of a CB2 receptor agonist [109]. Another study found that paclitaxel induced significant upregulation in IL-1α, IL-1β, IL-6, TNF-α, INF-γ and MCP-1, which was attenuated by a TNF-alpha monoclonal antibody (etanercept) [1] In a vincristine CIPN model, the anti-inflammatory cytokine, IL-4, and associated STAT signalling was reduced, with an increase in pro-inflammatory cytokines such as IL-1-beta and TNF-alpha [92]. IL-10, an anti-inflammatory cytokine, may be important in recovery from CIPN, with preclinical evidence from both platinum and taxane-related CIPN [63].…”

Section: Mechanismsmentioning

confidence: 98%

Chemotherapy-induced peripheral neuropathy: where are we now?

Colvin

2019

PAIN

169

131

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Chemotherapy induced peripheral neuropathy (CIPN) is a major challenge, with increasing impact as oncological treatments, using potentially neurotoxic chemotherapy, improve cancer cure and survival. Acute CIPN occurs during chemotherapy, sometimes requiring dose reduction or cessation, impacting on survival. Around 30% of patients will still have CIPN a year, or more, after finishing chemotherapy. Accurate assessment is essential to improve knowledge around prevalence and incidence of CIPN. Consensus is needed to standardize assessment and diagnosis, with use of well validated tools, such as the EORTC-CIPN 20. Detailed phenotyping of the clinical syndrome moves towards a precision medicine approach, to individualize treatment. Understanding significant risk factors and pre-existing vulnerability may be used to improve strategies for CIPN prevention, or to use targeted treatment for established CIPN. No preventive therapies have shown significant clinical efficacy, although there are promising novel agents such as histone deacetylase 6 (HDAC6) inhibitors, currently in early phase clinical trials for cancer treatment. Drug repurposing, e.g. metformin, may offer an alternative therapeutic avenue. Established treatment for painful CIPN is limited. Following recommendations for general neuropathic pain is logical, but evidence for agents such as gabapentinoids and amitriptyline is weak. The only agent currently recommended by the American Society of Clinical Oncology is duloxetine. Mechanisms are complex with changes in ion channels (sodium, potassium and calcium), Transient Receptor Potential (TRP) channels, mitochondrial dysfunction, and immune cell interactions. Improved understanding is essential to advance CIPN management. On a positive note, there are many potential sites for modulation, with novel analgesic approaches.

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Section: Mechanismsmentioning

confidence: 98%

Chemotherapy-induced peripheral neuropathy: where are we now?

Colvin

2019

PAIN

169

131

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“…The neuroprotective effect of IL-4 may be achieved by stimulating IL-4/STAT6 signal transduction and inhibiting pro-inflammatory cytokines. Previous study has showed that IL-4 knockout mice produce more pro-inflammatory cytokines, including IL-1β and TNF-α ( 40 ). The loss of IL-4 in mice also increases sensitivity to mechanical pain.…”

Section: Il-4mentioning

confidence: 99%

“…IL-4 is required for female neuroprotection during the estrus phase of the estrus cycle ( 38 ). In protected female WT mice, microglia/macrophages were dominated by M2 polarization and inflammatory infiltration was reduced ( 40 ). Therefore, increasing macrophage M2 polarization, with or without added inhibition of inflammatory infiltration, may be a novel approach for stroke treatment.…”

Section: Il-4mentioning

confidence: 99%

Interleukins and Ischemic Stroke

Zhu

et al. 2022

Front. Immunol.

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Ischemic stroke after cerebral artery occlusion is one of the major causes of chronic disability worldwide. Interleukins (ILs) play a bidirectional role in ischemic stroke through information transmission, activation and regulation of immune cells, mediating the activation, multiplication and differentiation of T and B cells and in the inflammatory reaction. Crosstalk between different ILs in different immune cells also impact the outcome of ischemic stroke. This overview is aimed to roughly discuss the multiple roles of ILs after ischemic stroke. The roles of IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL-16, IL-17, IL-18, IL-19, IL-21, IL-22, IL-23, IL-32, IL-33, IL-34, IL-37, and IL-38 in ischemic stroke were discussed in this review.

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“…The re-introduction of IL-4 attenuated also p-STAT6 down-regulation suggesting IL-4 protective role towards VIPN via the stimulation of IL-4/STAT6 signaling pathway. Moreover, the over-expression of the pro-inflammatory cytokines IL-1β and TNF-α was reported in IL-4 KO animals compared to the wild type control mice ( 172 ).…”

Section: Introductionmentioning

confidence: 99%

Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy

et al. 2021

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Peripheral neuropathies are characterized by nerves damage and axonal loss, and they could be classified in hereditary or acquired forms. Acquired peripheral neuropathies are associated with several causes, including toxic agent exposure, among which the antineoplastic compounds are responsible for the so called Chemotherapy-Induced Peripheral Neuropathy (CIPN). Several clinical features are related to the use of anticancer drugs which exert their action by affecting different mechanisms and structures of the peripheral nervous system: the axons (axonopathy) or the dorsal root ganglia (DRG) neurons cell body (neuronopathy/ganglionopathy). In addition, antineoplastic treatments may affect the blood brain barrier integrity, leading to cognitive impairment that may be severe and long-lasting. CIPN may affect patient quality of life leading to modification or discontinuation of the anticancer therapy. Although the mechanisms of the damage are not completely understood, several hypotheses have been proposed, among which neuroinflammation is now emerging to be relevant in CIPN pathophysiology. In this review, we consider different aspects of neuro-immune interactions in several CIPN preclinical studies which suggest a critical connection between chemotherapeutic agents and neurotoxicity. The features of the neuroinflammatory processes may be different depending on the type of drug (platinum derivatives, taxanes, vinca alkaloids and proteasome inhibitors). In particular, recent studies have demonstrated an involvement of the immune response (both innate and adaptive) and the stimulation and secretion of mediators (cytokines and chemokines) that may be responsible for the painful symptoms, whereas glial cells such as satellite and Schwann cells might contribute to the maintenance of the neuroinflammatory process in DRG and axons respectively. Moreover, neuroinflammatory components have also been shown in the spinal cord with microglia and astrocytes playing an important role in CIPN development. Taking together, better understanding of these aspects would permit the development of possible strategies in order to improve the management of CIPN.

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Interleukin-4 protects from chemotherapy-induced peripheral neuropathy in mice modal via the stimulation of IL-4/STAT6 signaling

Abstract: Anti-inflammatory cytokine IL-4 protects rodent model from vincristine-induced peripheral neuropathy via the stimulation of IL-4/STAT6 signaling and inhibition of the pro-inflammatory cytokines.

Cited by 15 publications

References 27 publications

Chemotherapy-induced peripheral neuropathy: where are we now?

Chemotherapy-induced peripheral neuropathy: where are we now?

Interleukins and Ischemic Stroke

Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy

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