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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

The effect of daily injections on the pharmacokinetics and biodistribution of PE.Notes: (A) Blood clearance. (B) Hepatic and splenic accumulation 12 hours after intravenous injection of the test dose. n days represent the nth-day PE injection. Data are shown as mean ± SD, n=3. P-values apply to differences between the control and treated rats; **P<0.01, ***P<0.001.Abbreviations: PE, PEGylated emulsion; PEG, polyethylene glycol; SD, standard deviation.
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f3-ijn-9-3645: The effect of daily injections on the pharmacokinetics and biodistribution of PE.Notes: (A) Blood clearance. (B) Hepatic and splenic accumulation 12 hours after intravenous injection of the test dose. n days represent the nth-day PE injection. Data are shown as mean ± SD, n=3. P-values apply to differences between the control and treated rats; **P<0.01, ***P<0.001.Abbreviations: PE, PEGylated emulsion; PEG, polyethylene glycol; SD, standard deviation.

Mentions: The influence of consecutive daily injections on the pharmacokinetics and biodistribution of PE was studied. As shown in Figure 3, blood clearance and hepatic and splenic accumulation significantly increased after 7 days of sequential injection (AUC ratio =0.10±0.01). An inverse correlation between the dose frequency and the magnitude of the ABC phenomenon was observed. The ABC phenomenon was avoided after 21 days of consecutive administrations. Interestingly, the blood elimination rate of PE injected after 21 days was less than a single dose (AUC ratio =1.37±0.11, P<0.05).


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)

The effect of daily injections on the pharmacokinetics and biodistribution of PE.Notes: (A) Blood clearance. (B) Hepatic and splenic accumulation 12 hours after intravenous injection of the test dose. n days represent the nth-day PE injection. Data are shown as mean ± SD, n=3. P-values apply to differences between the control and treated rats; **P<0.01, ***P<0.001.Abbreviations: PE, PEGylated emulsion; PEG, polyethylene glycol; SD, standard deviation.
© Copyright Policy
Related In: Results  -  Collection

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

f3-ijn-9-3645: The effect of daily injections on the pharmacokinetics and biodistribution of PE.Notes: (A) Blood clearance. (B) Hepatic and splenic accumulation 12 hours after intravenous injection of the test dose. n days represent the nth-day PE injection. Data are shown as mean ± SD, n=3. P-values apply to differences between the control and treated rats; **P<0.01, ***P<0.001.Abbreviations: PE, PEGylated emulsion; PEG, polyethylene glycol; SD, standard deviation.
Mentions: The influence of consecutive daily injections on the pharmacokinetics and biodistribution of PE was studied. As shown in Figure 3, blood clearance and hepatic and splenic accumulation significantly increased after 7 days of sequential injection (AUC ratio =0.10±0.01). An inverse correlation between the dose frequency and the magnitude of the ABC phenomenon was observed. The ABC phenomenon was avoided after 21 days of consecutive administrations. Interestingly, the blood elimination rate of PE injected after 21 days was less than a single dose (AUC ratio =1.37±0.11, P<0.05).

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