Tongtong Zhao1,2, Kai Zhang1,2, Yelei Zhang1,2, Yating Yang1,2, Xiaoshuai Ning1,2, Yu Hu1,2, Xiaoyue Li1,2, Yulong Zhang1,2, Lei Xia1,2, Zhenhua Ren3, Huanzhong Liu4,5. 1. Department of Psychiatry, Chaohu Hospital of Anhui Medical University, 64 North Chaohu Road, Hefei, Anhui Province, China. 2. Anhui Psychiatric Center, Anhui Medical University, Hefei, Anhui Province, China. 3. Department of Anatomy, Anhui Medical University, Road Hefei, Meishan, 81, Anhui Province, China. renzhenhua@ahmu.edu.cn. 4. Department of Psychiatry, Chaohu Hospital of Anhui Medical University, 64 North Chaohu Road, Hefei, Anhui Province, China. huanzhongliu@ahmu.edu.cn. 5. Anhui Psychiatric Center, Anhui Medical University, Hefei, Anhui Province, China. huanzhongliu@ahmu.edu.cn.
Abstract
RATIONALE AND OBJECTIVE: Clozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders. METHODS: We measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophrenia patients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue. RESULTS: Following clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-β levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1β, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients' BMI, blood glucose, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1β and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α. CONCLUSION: Findings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.
RATIONALE AND OBJECTIVE:Clozapine (CLZ) is the most effective drug for treatment-resistant schizophrenia but is associated with many side effects, including glycometabolism disorders. Immunological mechanisms may be involved in the development of clozapine side effects. Research relating the immunomodulatory effects of clozapine and its early markers to clinically relevant adverse events is needed to reduce the harmful side effects of clozapine. This study aimed to investigate the role of proinflammatory cytokines in clozapine-associated glycometabolism disorders. METHODS: We measured the effect of a range of doses of clozapine on glycometabolism-related parameters and proinflammatory cytokines levels in mice peripheral blood. We also examined the differences between these indicators in the peripheral blood of clozapine-treated schizophreniapatients and healthy controls. Furthermore, we detected proinflammatory cytokines expression in mice pancreatic tissue. RESULTS: Following clozapine administration, glucagon significantly decreased in mouse serum, and proinflammatory cytokine IL-β levels markedly increased. Clozapine reliably increased proinflammatory cytokines (IL-1β, IL-6, and TNF-α) expression in murine pancreatic tissue. Compared with healthy controls, clozapine-treated patients' BMI, blood glucose, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) increased significantly. In clozapine-treated patients, a higher clozapine daily dosage was associated with higher levels of the proinflammatory cytokines IL-1β and IL-6, and a significant positive correlation was observed between blood glucose levels and the proinflammatory cytokines IL-6 and TNF-α. CONCLUSION: Findings from animal experiments and clinical trials have shown clear evidence that clozapine has a regulatory effect on immune-related proinflammatory cytokines and influences glycometabolism indicators.
Authors: Wouter Beumer; Roosmarijn C Drexhage; Harm De Wit; Marjan A Versnel; Hemmo A Drexhage; Dan Cohen Journal: Psychoneuroendocrinology Date: 2012-04-27 Impact factor: 4.905
Authors: Louise Benarroch; Chantel Kowalchuk; Virginia Wilson; Celine Teo; Melanie Guenette; Araba Chintoh; Yasika Nesarajah; Valerie Taylor; Peter Selby; Paul Fletcher; Gary J Remington; Margaret K Hahn Journal: Psychopharmacology (Berl) Date: 2016-06-01 Impact factor: 4.530