Tolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions

Long Wang,* Chunling Wang,* Jiao Jiao, Yuqing Su, Xiaobo Cheng, Zhenjun Huang, Xinrong Liu, Yihui DengCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China*These authors contributed equally to this workAbstract: There has been an increasing interest...

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Autores principales:	Wang L, Wang C, Jiao J, Su Y, Cheng X, Huang Z, Liu X, Deng Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6b3e172dd0324ed782b61ef0d88122c0
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spelling	oai:doaj.org-article:6b3e172dd0324ed782b61ef0d88122c02021-12-02T02:10:35ZTolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions1178-2013https://doaj.org/article/6b3e172dd0324ed782b61ef0d88122c02014-08-01T00:00:00Zhttp://www.dovepress.com/tolerance-like-innate-immunity-and-spleen-injury-a-novel-discovery-via-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Long Wang,* Chunling Wang,* Jiao Jiao, Yuqing Su, Xiaobo Cheng, Zhenjun Huang, Xinrong Liu, Yihui DengCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China*These authors contributed equally to this workAbstract: There has been an increasing interest in the study of the innate immune system in recent years. However, few studies have focused on whether innate immunity can acquire tolerance. Therefore, in this study, we investigated tolerance in the innate immune system via the consecutive weekly and daily injections of emulsions modified with polyethylene glycol (PEG), referred to as PEGylated emulsions (PE). The effects of these injections of PE on pharmacokinetics and biodistribution were studied in normal and macrophage-depleted rats. Additionally, we evaluated the antigenic specificity of immunologic tolerance. Immunologic tolerance against PE developed after 21 days of consecutive daily injections or the fourth week of PE administration. Compared with a single administration, it was observed that the tolerant rats had a lower rate of PE clearance from the blood, which was independent of the stress response. In addition, weekly PE injections caused injury to the spleen. Furthermore, the rats tolerant to PEs with the methoxy group (-OCH3) of PEG, failed to respond to the PEs with a different terminal group of PEG or to non-PEG emulsions. Innate immunity tolerance was induced by PE, regardless of the mode of administration. Further study of this mechanism suggested that monocytes play an essential role in the suppression of innate immunity. These findings provide novel insights into the understanding of the innate immune system.Keywords: immunologic tolerance, innate immune system, pharmacokinetics, biodistribution, antigenic specificityWang LWang CJiao JSu YCheng XHuang ZLiu XDeng YDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 3645-3657 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Wang L Wang C Jiao J Su Y Cheng X Huang Z Liu X Deng Y Tolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions
description	Long Wang,* Chunling Wang,* Jiao Jiao, Yuqing Su, Xiaobo Cheng, Zhenjun Huang, Xinrong Liu, Yihui DengCollege of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China*These authors contributed equally to this workAbstract: There has been an increasing interest in the study of the innate immune system in recent years. However, few studies have focused on whether innate immunity can acquire tolerance. Therefore, in this study, we investigated tolerance in the innate immune system via the consecutive weekly and daily injections of emulsions modified with polyethylene glycol (PEG), referred to as PEGylated emulsions (PE). The effects of these injections of PE on pharmacokinetics and biodistribution were studied in normal and macrophage-depleted rats. Additionally, we evaluated the antigenic specificity of immunologic tolerance. Immunologic tolerance against PE developed after 21 days of consecutive daily injections or the fourth week of PE administration. Compared with a single administration, it was observed that the tolerant rats had a lower rate of PE clearance from the blood, which was independent of the stress response. In addition, weekly PE injections caused injury to the spleen. Furthermore, the rats tolerant to PEs with the methoxy group (-OCH3) of PEG, failed to respond to the PEs with a different terminal group of PEG or to non-PEG emulsions. Innate immunity tolerance was induced by PE, regardless of the mode of administration. Further study of this mechanism suggested that monocytes play an essential role in the suppression of innate immunity. These findings provide novel insights into the understanding of the innate immune system.Keywords: immunologic tolerance, innate immune system, pharmacokinetics, biodistribution, antigenic specificity
format	article
author	Wang L Wang C Jiao J Su Y Cheng X Huang Z Liu X Deng Y
author_facet	Wang L Wang C Jiao J Su Y Cheng X Huang Z Liu X Deng Y
author_sort	Wang L
title	Tolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions
title_short	Tolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions
title_full	Tolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions
title_fullStr	Tolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions
title_full_unstemmed	Tolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions
title_sort	tolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of pegylated emulsions
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/6b3e172dd0324ed782b61ef0d88122c0
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Tolerance-like innate immunity and spleen injury: a novel discovery via the weekly administrations and consecutive injections of PEGylated emulsions

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