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

概述恒河猴(Macaca mulatta)实验性革兰氏阴性脓毒症模型早期阶段的关键炎症相关参数

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作者:Jose J Rosado-Franco, Marcos J Ramos-Benitez, Laura M Parodi, Derick Rosario, Nicole Compo, Luis D Giavedoni, Ana M Espino

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.

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