Changes of inflammation-associated cytokine expressions during early phase of experimental endotoxic shock in

Xiao-Hui Ji1, Ke-Yi Sun, Yan-Hong Feng

  • 1Department of Microbiology and Immunology, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. immune@njmu.edu.cn

Abstract

Insights

This study successfully modeled endotoxic shock in macaques, revealing early release of key inflammatory cytokines like tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) within 120 minutes. Peripheral blood mononuclear cells and liver cells were identified as significant sources of these crucial inflammatory mediators.

Area of Science:

  • Immunology
  • Pathophysiology
  • Primate Models

Background:

  • Endotoxemia, induced by lipopolysaccharide (LPS), triggers a systemic inflammatory response.
  • Understanding early cytokine dynamics is crucial for developing targeted therapies for endotoxic shock.

Purpose of the Study:

  • To investigate the expression patterns of inflammation-associated cytokines during the early stages of endotoxic shock in macaques.
  • To establish a reliable macaque model for studying endotoxic shock.

Main Methods:

  • Macaque mulatta were administered LPS to induce endotoxic shock, with blood and tissue samples collected at various time points.
  • Plasma cytokine levels (TNF-alpha, IL-1beta, IL-10, IL-12P40) were measured using ELISA.
  • mRNA expression of TNF-alpha, IL-1beta, and IL-18 in PBMCs, liver, and spleen was analyzed via RT-PCR.

Main Results:

  • LPS administration led to a significant decrease in mean arterial pressure and hemodynamic parameters.
  • Plasma levels of TNF-alpha and IL-10 increased within 60 minutes, while IL-1beta and IL-12P40 rose by 120 minutes.
  • Elevated mRNA levels of TNF-alpha, IL-1beta, and IL-18 were observed in PBMCs and liver tissues early in the shock phase.

Conclusions:

  • A macaque model of endotoxic shock was successfully established using LPS.
  • Human cytokine assays proved effective for macaque cytokine detection.
  • Early release of multiple inflammatory and anti-inflammatory cytokines was confirmed within 120 minutes post-LPS, with PBMCs and liver cells as key sources.