Effect of solid lipid nanoparticles (SLN) on cytokine production and the viability of murine peritoneal macrophages.
The purpose of this study was to investigate possible immunomodulatory and cytotoxic effects of solid lipid nanoparticles (SLN) on murine peritoneal macrophages. Immunomodulatory effects of SLN composed of either a lipid- (glycerol-behenate) or a wax (cetylpalmitate) matrix stabilized by the surfactant Poloxamer 188 were analysed by detection of proinflammatory and down-regulatory cytokines in supernatants of thioglycollate-elicited peritoneal macrophages using enzyme-linked immunosorbent assay (ELISA). Cytotoxicity of SLN was assessed using the ITT test. Incubation of macrophages with either SLN at low concentrations did not increase production of interleukin (IL)-6, IL-12, and tumour necrosis factor (TNF)-alpha. At higher SLN concentrations, a concentration-dependent decrease in IL-6 secretion was observed compared to background production of IL-6 by untreated macrophages. IL-12 and TNF-alpha production was neither detected in supernatants of macrophages treated with SLN at any concentration nor in those of untreated cells. The decrease in IL-6 secretion was paralleled by concentration-dependent cytotoxicity of SLN on these cells. In contrast, incubation with polystyrene reference particles neither resulted in decreased IL-6 production nor in a loss of viability. SLN-treated macrophages were found to up-regulate their cytokine production following stimulation with Pansorbin, despite the concentration-dependent cytotoxicity induced by SLN. Down-regulatory effects on SLN-treated macrophages by IL-10 were not observed. In conclusion, incubation of SLN with murine peritoneal macrophages did not induce the production of proinflammatory and down-regulatory cytokines. At high concentrations of SLN, cytotoxic effects on these cells were observed. Cytotoxicity appears to be the main cause of decreased cytokine production by these cells.
Schöler
N
N
Department of Medical Microbiology, Benjamin Franklin Medical Center, Free University of Berlin, Germany.
Zimmermann
E
E
Katzfey
U
U
Hahn
H
H
Müller
R H
RH
Liesenfeld
O
O
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002214:Capsules / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008055:Lipids; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000276:Adjuvants, Immunologic; D002214:Capsules; D016207:Cytokines; D015850:Interleukin-6; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12