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Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders?
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 immuno...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233252/ https://www.ncbi.nlm.nih.gov/pubmed/33774704 http://dx.doi.org/10.1007/s00213-021-05824-9 |
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author | Zhao, Tongtong Zhang, Kai Zhang, Yelei Yang, Yating Ning, Xiaoshuai Hu, Yu Li, Xiaoyue Zhang, Yulong Xia, Lei Ren, Zhenhua Liu, Huanzhong |
author_facet | Zhao, Tongtong Zhang, Kai Zhang, Yelei Yang, Yating Ning, Xiaoshuai Hu, Yu Li, Xiaoyue Zhang, Yulong Xia, Lei Ren, Zhenhua Liu, Huanzhong |
author_sort | Zhao, Tongtong |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8233252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-82332522021-07-09 Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders? Zhao, Tongtong Zhang, Kai Zhang, Yelei Yang, Yating Ning, Xiaoshuai Hu, Yu Li, Xiaoyue Zhang, Yulong Xia, Lei Ren, Zhenhua Liu, Huanzhong Psychopharmacology (Berl) Original Investigation 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. Springer Berlin Heidelberg 2021-03-27 2021 /pmc/articles/PMC8233252/ /pubmed/33774704 http://dx.doi.org/10.1007/s00213-021-05824-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Investigation Zhao, Tongtong Zhang, Kai Zhang, Yelei Yang, Yating Ning, Xiaoshuai Hu, Yu Li, Xiaoyue Zhang, Yulong Xia, Lei Ren, Zhenhua Liu, Huanzhong Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders? |
title | Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders? |
title_full | Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders? |
title_fullStr | Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders? |
title_full_unstemmed | Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders? |
title_short | Do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders? |
title_sort | do proinflammatory cytokines play a role in clozapine-associated glycometabolism disorders? |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233252/ https://www.ncbi.nlm.nih.gov/pubmed/33774704 http://dx.doi.org/10.1007/s00213-021-05824-9 |
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