%0 Journal Article
%T Comparison of different lots of endotoxin and evaluation of in vivo potency over time in the experimental human endotoxemia model
%A Dorien Kiers
%A Guus P. Leijte
%A Jelle Gerretsen
%A Jelle Zwaag
%A Matthijs Kox
%A Peter Pickkers
%J Innate Immunity
%@ 1753-4267
%D 2019
%R 10.1177/1753425918819754
%X The experimental human endotoxemia model is used to study the systemic inflammatory response in vivo. The previously used lot of endotoxin, which was used for over a decade, is no longer approved for human use and a new Good Manufacturing Practices-grade batch has become available. We compared the inflammatory response induced by either bolus or continuous administration of either the previously used lot #1188844 or new lots of endotoxin (#94332B1 and #94332B4). Compared with lot #1188844, bolus administration of lot #94332B1 induced a more pronounced systemic inflammatory response including higher plasma levels of pro-inflammatory cytokines and more pronounced clinical signs of inflammation. In contrast, continuous infusion of lot #94332B4 resulted in a slightly less pronounced inflammatory response compared with lot #1188844. Furthermore, we evaluated whether lot #1188844 displayed in vivo potency loss by reviewing inflammatory parameters obtained from 17 endotoxemia studies performed in our centre between 2007 and 2016. Despite inter-study variability in endotoxemia-induced effects on temperature, heart rate, symptoms, and leukocyte counts, the magnitude of these effects did not decrease over time. In conclusion, although all lots of endotoxin induce a pronounced inflammatory response, the magnitude differs between lots. We observed no potency loss of endotoxin over time
%K Endotoxemia
%K in vivo
%K lipopolysaccharide
%K potency
%K systemic inflammation
%U https://journals.sagepub.com/doi/full/10.1177/1753425918819754