OVERPRODUCED PRO-INFLAMMATORY CYTOKINES IS POSITIVELY CORRELATED WITH THE EXPRESSION OF TLR4/TDAG8 MRNA IN SEPSIS

In-depth understanding of the pathophysiological mechanisms and discovery of important mediators involved in the process of sepsis is urgently needed. A rat sepsis model was induced by intraperitoneal injection of lipopolysaccharide (LPS; 25 mg/kg/body weight). The acute lung injury of rats after LPS stimulation was detected by haematoxylin-eosin staining and the lung wet-to-dry weight ratio. The contents of MCP-1, IL-6, IL-21 and CXCL-8 in rat peripheral blood were measured using ELISA kits. The mRNA expression of Toll-like receptor-4 (TLR4) and T-cell death-associated gene 8 (TDAG8) were determined by RT-qPCR. Finally, the linear correlation analysis was performed to explain the correlation between TDAG8/TLR4 mRNA and IL-6, as well as other pro-inflammatory mediators. The data showed that LPS stimulation had no effect on rat body weight, but led to severe lung injury. Furthermore, LPS enhanced the production of IL-6, CXCL-8, IL-21 and MCP-1 more than three-fold and remarkably elevated the expression of TDAG8 and TLR4 mRNA (p<0.001). However, on day 7, the concentrations of these four pro-inflammatory cytokines and expression of TLR4/TDAG8 mRNA exhibited a slight decrease compared with those of day 1; however, they still remained at high levels compared with normal control rats (p<0.001). The expression of TDAG8 and TLR4 mRNA were enhanced gradually with an increase in the production of pro-inflammatory mediators. Altogether, the rapid and marked rise of IL-6, MCP-1, IL-21 and CXCL-8 combined with TLR4/TADG8 overexpression revealed the effective prognostic value for sepsis.