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

Abstract

Abstract Sepsis is a life-threatening syndrome characterized by metabolic and systemic dysregulation in the presence of an invading pathogen, such as bacteria or fungi. In the initial stages of this syndrome, the body, in an attempt to eradicate the pathogen, secretes high levels of pro-inflammatory cytokines and chemokines that leads to an anti-inflammatory state, which leads to organ dysfunction and death. Despite the efforts to find targeted therapeutics to treat septic patients, physicians rely on the administration of antibiotics and fluids. Hence, the development of novel targeted therapeutics to treat septic patients at early stages of sepsis is highly important to save the lives of these patients. The aim of this study was to identify inflammation markers during the early phase of sepsis in rhesus macaque. Four rhesus macaque were given an intravenous dose of 1010 CFU/kg of E. coli. Blood samples were collected before, 30 minutes, 2, 4, 6 and 8 hours after E. coli infusion. Physiological parameters, bacteremia, endotoxemia, C-reactive protein (CRP), procalcitonin (PCT), and cytokines and chemokines were determined for each animal at each time point. Bacteremia was present in all animals from 30 minutes to 3 hours after E. coli infusion. Endotoxin, CRP and PCT levels remained detectable during the whole experimental window. Signature cytokines and chemokines such as TNFα, MIP1α, and MIP1β peaked about 2 hours after E. coli infusion and decreased thereafter. Plasma IL6, IL12p40, IFNγ, and IL1Ra, ITAC, MIG, IP10 and MCP1, remained at detectable levels after 4 hours of E. coli infusion. This non-human primate model could be useful for the assessment of new therapeutics aiming to suppress key inflammatory markers throughout sepsis early phases.