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 m acrophages. Immunomodulatory effects of SLN composed of either a lipid( gly cerol-behenate) or a wax (cetylpalmitate) matrix stabilized by the surfacta nt Poloxamer 188 were analysed by detection of proinflammatory and down-reg ulatory cytokines in supernatants of thioglycollate-elicited peritoneal mac rophages using enzyme-linked immunosorbent assay (ELISA). Cytotoxicity of S LN was assessed using the MTT test. Incubation of macrophages with either S LN at low concentrations did not increase production of interleukin (IL)-6, IL-12, and tumour necrosis factor (TNF)-alpha. At higher SLN concentration s, a concentration-dependent decrease in IL-6 secretion was observed compar ed to background production of IL-6 by untreated macrophages. IL-12 and TNF -alpha production was neither detected in supernatants of macrophages treat ed with SLN at any concentration nor in those of untreated cells. The decre ase in IL-6 secretion was paralleled by concentration-dependent cytotoxicit y of SLN on these cells. In contrast, incubation with polystyrene reference particles neither resulted in decreased IL-6 production nor in a loss of v iability. 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-treat ed macrophages by IL-10 were not observed. In conclusion, incubation of SLN with murine peritoneal macrophages did not induce the production of proinf lammatory and down-regulatory cytokines. At high concentrations of SLN, cyt otoxic effects on these cells were observed. Cytotoxicity appears to be the main cause of decreased cytokine production by these cells.