title: Effect of solid lipid nanoparticles (SLN) on cytokine production and the viability of murine peritoneal macrophages.
abstract: 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.
authors.affiliation: Department of Medical Microbiology, Benjamin Franklin Medical Center, Free University of Berlin, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Schöler
authors.forename: E
authors.initials: E
authors.lastname: Zimmermann
authors.forename: U
authors.initials: U
authors.lastname: Katzfey
authors.forename: H
authors.initials: H
authors.lastname: Hahn
authors.forename: R H
authors.initials: RH
authors.lastname: Müller
authors.forename: O
authors.initials: O
authors.lastname: Liesenfeld
mesh_terms: 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
chemical_list: D000276:Adjuvants, Immunologic; D002214:Capsules; D016207:Cytokines; D015850:Interleukin-6; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12