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类先天免疫耐受和脾损伤：一个新给药途径，通过按周给药和连续注射聚乙二醇乳液

 

Authors Wang L, Wang C, Jiao J, Su Y, Cheng X, Huang Z, Liu X, Deng Y

Published Date August 2014 Volume 2014:9(1) Pages 3645—3657

DOI http://dx.doi.org/10.2147/IJN.S66318

Received 16 April 2014, Accepted 24 May 2014, Published 4 August 2014

Abstract: 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






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