Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?
| Autor: | Tongtong Zhao, Yulong Zhang, Lei Xia, Yating Yang, Yelei Zhang, Kai Zhang, Xiaoshuai Ning, Huanzhong Liu, Xiaoyue Li, Zhenhua Ren, Yu Hu |
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| Rok vydání: | 2020 |
| Předmět: |
Drug
Adult Blood Glucose Male Immunomodulatory media_common.quotation_subject Glucagon Proinflammatory cytokine 03 medical and health sciences Mice 0302 clinical medicine Metabolic Diseases Medicine Animals Humans Adverse effect Clozapine 030304 developmental biology media_common Original Investigation Pharmacology 0303 health sciences business.industry Pancreatic tissue Tumor Necrosis Factor-alpha Middle Aged medicine.disease Peripheral blood Mice Inbred C57BL Schizophrenia Immunology Cytokines Glycometabolism disorders Inflammation Mediators business 030217 neurology & neurosurgery medicine.drug Antipsychotic Agents |
| Zdroj: | Psychopharmacology |
| ISSN: | 1432-2072 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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