Effect of transforming growth factor-β1 on monocyte Toll-like receptor 4 expression in septic rats

Sepsis is a tough problem in critical ill patients. This study aimed to investigate the dynamic changes of monocyte Toll-like receptor (TLR) 4 expression in peripheral blood of septic rats and to determine the effects of transforming growth factor (TGF)-β1 on TLR4 expression.

Altogether 132 clean level SD rats were randomly divided into a control group (n=12), a sepsis model group (n=60), and a TGF-β1 intervention group (n=60). In the sepsis model group and TGF-β1 intervention group, the rats were subdivided into five groups (2-hour group, 6-hour group, 12-hour group, 24-hour group, and 48-hour group), with 12 rats in each group. Cecal ligation puncture (CLP) was performed in the sepsis model group and TGF-β1 intervention group to establish models of sepsis. The rats in the sepsis model group were injected with 1 mL normal saline at the caudal vein 0.5 hour after the model establishment; the rats in the TGF-β1 intervention group were injected with 20 ng/mL or 250 g TGF-β1 0.5 hour after the model establishment. Flow cytometry was used to detect the change of monocyte TLR4 in peripheral blood, and enzyme-linked immunosorbent assay (ELISA) was used to detect the change of TNF-α level in peripheral blood.

At 6-12 hours after CLP, the monocyte TLR4 in peripheral blood started to decrease, and reached the lowest level at 12 hours. Compared to the control group, the monocyte TLR4 expression at 6 and 12 hours was lowered significantly (P<0.05). Compared to the sepsis model group at 2, 24 and 48 hours after CLP, the monocyte TLR4 expression in the TGF-β1 intervention group decreased dramatically (P<0.05), but there were no differences between the two groups at 6 and 12 hours respectively. Compared to the control group, the concentration of NF-κ in liver tissue increased significantly 6 hours after CLP (P<0.05). After use of TGF-β1, the concentration of NF-κ was decreased significantly but still higher than that of the control group. Compared to the control group, the concentration of TNF-α in peripheral blood was increased significantly at 2-48 hours after CLP (P<0.05). After use of TGF-β1, TNF-α was further increased.

During sepsis, TGF-β1 can decrease the monocyte TLR4 expression and NF-κ in liver tissue, but facilitate the formation of proinflammatory mediator TNF-α. This finding indicates that TGF-β1 may play a role in promoting inflammatory response during sepsis, but this regulation is not via direct regulation of monocyte TLR4 in peripheral blood.