Real-time detection of LPS induced cytokine-storm using Vium Smart Housing

Abstract

Abstract The objective of this study was to use Vium Smart Housing to determine if in-life digital readouts (e.g. changes in motion and breathing rate) can correlate with cytokine response profiles in an LPS-induced mouse model of endotoxemia. Real-time detection of cytokine release has the potential to reduce or eliminate the need for expensive blood sampling and biochemical analyses. Eighty Balb/c mice were injected with 5 mg/kg of UltraPure LPS (E. coli 0111:B4, Invivogen) or vehicle control. Subjects were housed in Vium’s Digital Vivarium, where sensors and a HD camera coupled with computer vision, data algorithms, and cloud capabilities allow for continuous monitoring of animals and collection of automated metrics such as motion, % time running on wheel and breathing rate. All study data is available in real-time. As early as 1 hr post-LPS administration, breathing rate increased from baseline, peaked 7 hours post-induction (8.7%±3.5% vehicle vs 39.5±3.1% LPS treated) and remained elevated relative to vehicle for over 24 hrs (p<0.05). Breathing rate changes were accompanied by decreased motion as early as 1 hr post-LPS administration, peaked at 2 hours post-induction (28.73%±53.2% vehicle vs –82.69%±1.72% LPS treated), and remained decreased for over 24 hrs (p<0.05). Increased breathing positively correlated, while decreased motion negatively correlated with plasma levels of TNFα, and IL-10 at 1.5 hrs, and IL-6, IL-1B, and IFN-γ levels at 6 hrs post-LPS (p<0.05). We found that Vium’s automated metrics was able to detect onset of LPS-induced endotoxemia in real-time. This could be used to 1) screen compounds that prevent immune responses or alternatively 2) to identify cytokine release syndrome when screening immuno-oncology candidates.