SEPSIS-INDUCED CASCADE OF CYTOKINE MESSENGER-RNA EXPRESSION - CORRELATION WITH METABOLIC CHANGES

The relationships between metabolic alterations and tissue-specific gene expression of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), gamma-interferon (gamma-IFN), and interleukin 1 and serum levels of TNF-alpha and IL-6 before and after a live Escherichia coli septic challenge to rats were examined. From 0 to 2 h, serum glucose significantly decreased while plasma glucagon increased. By 8 h, plasma glucagon, serum insulin, and glucose appearance were significantly elevated. Gene expression of phosphoenolpyruvate carboxykinase increased 1 h after E. coli but by 4 h was significantly decreased. TNF-alpha mRNA (liver and spleen) and serum peptide levels peaked 1-2 h after the septic challenge and then decreased substantially by 6-8 h. Spleen IL-6 and gamma-IFN mRNA expression reached a maximum 4 h after E. coli challenge, whereas serum IL-6 levels were elevated by 2 h after injection of the bacteria. The increase in TNF-alpha mRNA and serum peptide levels correlated with the early fall in serum glucose and rise in plasma glucagon. Alterations in the rate of glucose appearance and plasma glucagon were observed later and coincided with the increased mRNA expression of IL-6 and gamma-IFN. Thus the metabolic alterations observed in the septic rat are associated with a complex cascade of several cytokines.