Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhao, Tongtong, Zhang, Kai, Zhang, Yelei, Yang, Yating, Ning, Xiaoshuai, Hu, Yu, Li, Xiaoyue, Zhang, Yulong, Xia, Lei, Ren, Zhenhua, Liu, Huanzhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
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
_version_ 1783713809480810496
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
work_keys_str_mv AT zhaotongtong doproinflammatorycytokinesplayaroleinclozapineassociatedglycometabolismdisorders
AT zhangkai doproinflammatorycytokinesplayaroleinclozapineassociatedglycometabolismdisorders
AT zhangyelei doproinflammatorycytokinesplayaroleinclozapineassociatedglycometabolismdisorders
AT yangyating doproinflammatorycytokinesplayaroleinclozapineassociatedglycometabolismdisorders
AT ningxiaoshuai doproinflammatorycytokinesplayaroleinclozapineassociatedglycometabolismdisorders
AT huyu doproinflammatorycytokinesplayaroleinclozapineassociatedglycometabolismdisorders
AT lixiaoyue doproinflammatorycytokinesplayaroleinclozapineassociatedglycometabolismdisorders
AT zhangyulong doproinflammatorycytokinesplayaroleinclozapineassociatedglycometabolismdisorders
AT xialei doproinflammatorycytokinesplayaroleinclozapineassociatedglycometabolismdisorders
AT renzhenhua doproinflammatorycytokinesplayaroleinclozapineassociatedglycometabolismdisorders
AT liuhuanzhong doproinflammatorycytokinesplayaroleinclozapineassociatedglycometabolismdisorders