The possibility that engineered nanoparticles, even in the absence of direct toxicity, may interfere with the normal development of the innate defensive response may cause inadequate immunity and eventual pathological consequences. The possible interference of nanoparticles with the normal development of the innate/inflammatory response was evaluated with an in vitro model based on human primary monocytes, which reliably represents the human inflammatory response. The course of the physiological inflammatory reaction, from initiation and development to eventual resolution, was reproduced by exposing CD14+ human blood monocytes to a sequence of different microenvironmental conditions (CCL2, LPS, TNF?, IFN-?, 37°C vs. 39°C). A parallel culture model was set up, by varying the culture conditions, to mimic persistent pre-pathological inflammation. The effect of endotoxin-free Au nanoparticles (diameter 10 nm, 1.28 ?g/ml, 0.16 cm2/million cells) was assessed on the course of the inflammatory reaction in the two in vitro models. Gene expression and protein production were analysed at different time points for the inflammatory cytokines and receptors IL-1?, IL-1?, IL-1RI, IL-6, IL-18, IL-36? and CCL5, and for the anti-inflammatory factors IL-1Ra, IL-1RII and IL-18BP. Preliminary results show that Au nanoparticles are unable to affect in a significant fashion the course of either the physiological or the persistent inflammatory reaction in the in vitro monocyte-based models, suggesting that these nanoparticles do not alter the innate defensive ability of the human body. We conclude that the use of a valid and representative in vitro model of human inflammation may allow us to realistically investigating the effects of nanoparticles on inflammatory/innate immune responses, thereby being useful to predicting the immunological risk posed by engineered nanomaterials.
A human monocyte-based in vitro model for evaluating the effects of engineered nanoparticles on the course of an inflammatory defence reaction.
2014
Abstract
The possibility that engineered nanoparticles, even in the absence of direct toxicity, may interfere with the normal development of the innate defensive response may cause inadequate immunity and eventual pathological consequences. The possible interference of nanoparticles with the normal development of the innate/inflammatory response was evaluated with an in vitro model based on human primary monocytes, which reliably represents the human inflammatory response. The course of the physiological inflammatory reaction, from initiation and development to eventual resolution, was reproduced by exposing CD14+ human blood monocytes to a sequence of different microenvironmental conditions (CCL2, LPS, TNF?, IFN-?, 37°C vs. 39°C). A parallel culture model was set up, by varying the culture conditions, to mimic persistent pre-pathological inflammation. The effect of endotoxin-free Au nanoparticles (diameter 10 nm, 1.28 ?g/ml, 0.16 cm2/million cells) was assessed on the course of the inflammatory reaction in the two in vitro models. Gene expression and protein production were analysed at different time points for the inflammatory cytokines and receptors IL-1?, IL-1?, IL-1RI, IL-6, IL-18, IL-36? and CCL5, and for the anti-inflammatory factors IL-1Ra, IL-1RII and IL-18BP. Preliminary results show that Au nanoparticles are unable to affect in a significant fashion the course of either the physiological or the persistent inflammatory reaction in the in vitro monocyte-based models, suggesting that these nanoparticles do not alter the innate defensive ability of the human body. We conclude that the use of a valid and representative in vitro model of human inflammation may allow us to realistically investigating the effects of nanoparticles on inflammatory/innate immune responses, thereby being useful to predicting the immunological risk posed by engineered nanomaterials.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
