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HEPC-based liposomes trigger cytokine release from peripheral blood cells: effects of liposomal size, dose and lipid
Sayaka Yamamoto1, Tatsuhiro Ishida, Akiko Inoue
1Department of Pharmacokinetics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1, Sho-machi, 770-8505, Tokushima, Japan.
Insights
Liposome stimulation triggers the release of key cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), from human blood cells. Larger liposomes induce higher cytokine release, a process dependent on protein kinase signaling.
Area of Science:
- Immunology
- Nanotechnology
- Biochemistry
Background:
- Liposomes are widely used in drug delivery systems.
- Understanding the immune response to liposomes is crucial for their safe and effective application.
- Cytokine release is a key indicator of immune system activation.
Purpose of the Study:
- To investigate the immune response induced by liposome stimulation in human peripheral blood cells.
- To determine the effect of liposome size and lipid composition on cytokine release.
- To elucidate the signaling pathways involved in liposome-induced cytokine production.
Main Methods:
- Human peripheral blood cells were stimulated with liposomes of varying sizes and lipid compositions.
- Cytokine levels (IL-6, IL-10, IL-1beta, TNF-alpha, IFN-gamma) were measured using appropriate assays.
- The role of protein kinase-C (PKC), protein tyrosine kinase (PTK), and endocytosis pathways was assessed using specific inhibitors.
Main Results:
- Liposome stimulation induced the release of multiple cytokines: IL-6, IL-10, IL-1beta, TNF-alpha, and IFN-gamma.
- Larger liposomes resulted in significantly higher levels of cytokine induction compared to smaller ones.
- Lipid composition did not affect the degree of cytokine release, and serum was not required for this response.
- Cytokine release was dependent on protein kinase-C (PKC) and protein tyrosine kinase (PTK) signaling pathways, but not on endocytosis.
Conclusions:
- Liposome stimulation activates human peripheral blood cells to release a panel of cytokines.
- Liposome size is a critical factor influencing the magnitude of the immune response.
- Signal transduction via PKC and PTK pathways is essential for liposome-induced cytokine release.
- These findings offer valuable insights for designing safer liposomal drug delivery systems and managing potential cytokine induction.
Abstract:
The immune response caused by liposome stimulation was studied by assessing the level of several cytokines released from human peripheral blood cells. Liposome stimulation resulted in the release of IL-6, IL-10, IL-1beta, TNF-alpha and IFN-gamma. The size of the liposomes affected the degree of the cytokine releases with larger sized liposomes causing higher levels of cytokine induction. In addition, it appears that the lipid composition of liposomes had no effect on the degree of cytokine release. The release of cytokines occurred even in the absence of serum, suggesting that serum proteins did not contribute to liposome stimulation in peripheral blood cells. The release of cytokines induced by liposome stimulation was inhibited by the presence of either protein kinase-C (PKC) or protein tyrosine kinase (PTK) inhibitor, but not by the presence of an endocytosis inhibitor. This indicates that signal transduction via PKC or PTK is necessary, in order for human peripheral blood cells to release cytokines (IL-6, IL-10, IL-1beta, TNF-alpha and IFN-gamma) as the result of liposome stimulation. These quantitative data on the release of cytokines by liposomal stimulation provide useful information for the development of rational drug delivery systems and the safety of cytokine induction via the use of liposomes.
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