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

Wang L, Wang C, Jiao J, Su Y, Cheng X, Huang Z, Liu X, Deng Y - Int J Nanomedicine (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.

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.

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Related in: MedlinePlus

Time schedule for the experiment.Notes: (A) The consecutive injections of PE group, n days represent the nth-day PE injection. (B) The weekly injections of PE group, PE-n represents the nth-week PE injection. Black arrows indicate the injection of the blank PE, and blue arrows indicate the injection of PE.Abbreviations: PE, PEGylated emulsion; PEG, polyethylene glycol.
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f1-ijn-9-3645: Time schedule for the experiment.Notes: (A) The consecutive injections of PE group, n days represent the nth-day PE injection. (B) The weekly injections of PE group, PE-n represents the nth-week PE injection. Black arrows indicate the injection of the blank PE, and blue arrows indicate the injection of PE.Abbreviations: PE, PEGylated emulsion; PEG, polyethylene glycol.

Mentions: Male Wistar rats were randomly divided into four groups: those receiving 1) weekly administration of PE, 2) daily injections of PE, 3) 5% glucose injection (5% Glu), and 4) the non-treated control group not receiving any treatment. The rats receiving daily injections of PE were injected with the PEs without TN at a dose of 5 μmol phospholipids/kg. Three rats were killed on days 7, 11, 14, 17, and 21 after the respective injections. The rats receiving weekly administrations of PE were treated with PEs without TN at the same dose, 5 μmol phospholipids/kg; the rats in the 5% Glu group were given only an injection of glucose; and the control group did not receive any treatment. For each injection, three randomly selected rats from each group received the same dose of TN-labeled PEs to investigate the pharmacokinetics and biodistribution of PE. The injection schemes are presented in Figure 1. All the administrations were intravenously injected into the tail vein. At 0.0167, 0.083, 0.25, 0.5, 1.0, 4.0, 8.0, and 12.0 hours after the intravenous injections, blood samples were obtained via eye punctures, and the samples were centrifuged at 1,078× g for 10 minutes to separate the plasma. After obtaining the last blood sample at 12 hours, the livers and spleens were excised and rinsed in ice-cold normal saline. The blood samples and tissue samples were stored at −20°C for future use.


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

Wang L, Wang C, Jiao J, Su Y, Cheng X, Huang Z, Liu X, Deng Y - Int J Nanomedicine (2014)

Time schedule for the experiment.Notes: (A) The consecutive injections of PE group, n days represent the nth-day PE injection. (B) The weekly injections of PE group, PE-n represents the nth-week PE injection. Black arrows indicate the injection of the blank PE, and blue arrows indicate the injection of PE.Abbreviations: PE, PEGylated emulsion; PEG, polyethylene glycol.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128795&req=5

f1-ijn-9-3645: Time schedule for the experiment.Notes: (A) The consecutive injections of PE group, n days represent the nth-day PE injection. (B) The weekly injections of PE group, PE-n represents the nth-week PE injection. Black arrows indicate the injection of the blank PE, and blue arrows indicate the injection of PE.Abbreviations: PE, PEGylated emulsion; PEG, polyethylene glycol.
Mentions: Male Wistar rats were randomly divided into four groups: those receiving 1) weekly administration of PE, 2) daily injections of PE, 3) 5% glucose injection (5% Glu), and 4) the non-treated control group not receiving any treatment. The rats receiving daily injections of PE were injected with the PEs without TN at a dose of 5 μmol phospholipids/kg. Three rats were killed on days 7, 11, 14, 17, and 21 after the respective injections. The rats receiving weekly administrations of PE were treated with PEs without TN at the same dose, 5 μmol phospholipids/kg; the rats in the 5% Glu group were given only an injection of glucose; and the control group did not receive any treatment. For each injection, three randomly selected rats from each group received the same dose of TN-labeled PEs to investigate the pharmacokinetics and biodistribution of PE. The injection schemes are presented in Figure 1. All the administrations were intravenously injected into the tail vein. At 0.0167, 0.083, 0.25, 0.5, 1.0, 4.0, 8.0, and 12.0 hours after the intravenous injections, blood samples were obtained via eye punctures, and the samples were centrifuged at 1,078× g for 10 minutes to separate the plasma. After obtaining the last blood sample at 12 hours, the livers and spleens were excised and rinsed in ice-cold normal saline. The blood samples and tissue samples were stored at −20°C for future use.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China.

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.

Show MeSH
Related in: MedlinePlus