Qingbin Shi1, Xiuying Cai2, Guixiang Shi3, Xingle Lv4, Jinping Yu5, Feng Wang6. 1. MD, Doctor-in-charge, Department of Encephalopathy, Zhangqiu District, Traditional Chinese Medicine Hospital, China. Acquisition, analysis and interpretation of data; manuscript preparation. 2. MD, Doctor-in-charge, Department of Encephalopathy, Zhangqiu District, Traditional Chinese Medicine Hospital, China. Technical procedures, acquisition of data. 3. MD, Nurse-in-charge, Department of Encephalopathy, Zhangqiu District, Traditional Chinese Medicine Hospital, China. Technical procedures. 4. MD, Nurse practitioner, Department of Encephalopathy, Zhangqiu District, Traditional Chinese Medicine Hospital, China. Technical procedures. 5. MD, Physician, Department of Encephalopathy, Zhangqiu District, Traditional Chinese Medicine Hospital, China. Technical procedures. 6. MD, Chief Physician, Department of Encephalopathy, Zhangqiu District, Traditional Chinese Medicine Hospital, China. Conception and design of the study, manuscript preparation, final approval.
Abstract
PURPOSE: To investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. METHODS: The mouse model of vincristine-induced peripheral neuropathy and interleukin (IL)-4 knockout mice were utilized to investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Vincristine induced increased sensitivity to mechanical stimulation was measured by von Frey hair test 7 and 14 days after intraperitoneal administration of 0.1 mg/kg vincristine in mice. Relative expression levels of cytokines were detected by quantitative real-time PCR. STAT6 expression following vincristine treatment was assessed with western blotting. RESULTS: We discovered that IL-4/STAT6 signaling was down-regulated in vincristine-treated mice. Deletion of IL-4 in mice increased the sensitivity to mechanical allodynia. IL-4 knockout mice also produced more pro-inflammatory cytokines, including IL-1β and TNF-α. Notably, co-administration of exogenous recombination IL-4 significantly prevented vincristine-induced mechanical allodynia. CONCLUSION: 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.
PURPOSE: To investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. METHODS: The mouse model of vincristine-induced peripheral neuropathy and interleukin (IL)-4 knockout mice were utilized to investigate the possible role of IL-4 signaling pathway in vincristine-induced peripheral neuropathy. Vincristine induced increased sensitivity to mechanical stimulation was measured by von Frey hair test 7 and 14 days after intraperitoneal administration of 0.1 mg/kg vincristine in mice. Relative expression levels of cytokines were detected by quantitative real-time PCR. STAT6 expression following vincristine treatment was assessed with western blotting. RESULTS: We discovered that IL-4/STAT6 signaling was down-regulated in vincristine-treated mice. Deletion of IL-4 in mice increased the sensitivity to mechanical allodynia. IL-4 knockout mice also produced more pro-inflammatory cytokines, including IL-1β and TNF-α. Notably, co-administration of exogenous recombination IL-4 significantly prevented vincristine-induced mechanical allodynia. CONCLUSION: 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.