Outlining key inflammation-associated parameters during early phase of an experimental gram-negative sepsis model in rhesus macaques (Macaca mulatta).

Abstract

The aim of this study was to identify inflammation‐associated markers during the early phase of sepsis in rhesus macaque. Four rhesus macaques were given an intravenous dose of 1010 CFU/kg of E. coli. Blood samples were collected before, or 30 minutes, 2, 4, 6 and 8 hours after E. coli infusion. Physiological parameters, bacteremia, endotoxemia, C‐reactive protein (CRP), procalcitonin (PCT), and plasma cytokines/chemokines were determined for each animal. Bacteremia was present in all animals from 30 minutes to 3 hours after E. coli infusion whereas endotoxin was detected during the full‐time course. CRP and PCT levels remained at detectable levels during the whole experimental window suggesting an ongoing inflammatory process. Signature cytokines and chemokines such as TNF‐α, MIP‐1α, and MIP‐1β peaked about 2 hours after E. coli infusion and decreased thereafter. Plasma IL‐6, IL‐12p40, IFN‐γ, and IL‐1Ra, as well as I‐TAC, MIG, IP‐10 and MCP‐1, remained at detectable levels after 4 hours of E. coli infusion. This nonhuman primate model could be useful for the assessment of new therapeutics aiming to suppress key inflammatory markers throughout sepsis early phases.