Immune response to severe insults: reaction through Toll-like receptors

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The objective of our study was as follows. (1) To clarify the immune response to severe insults (such as Toll-like receptor reactivity) in patients with sepsis or trauma. (2) To evaluate the functional changes in cells, which participate in immune reaction and inflammatory response after severe insults.We found the following results in the present study.(1)Monocyte functions: The expression of Toll-like receptor 2 amd 4, and intracellular heme oxygenase-1 were both enhanced in monocytes from patients with severe SIRS. The intracellular cytokine produnction through Toll-like receptors was inhibited in the patients. The heme oxygenase-1 expression in monocytes from healthy volunteers was enhanced when stimulated with the patients' serum. These results suggest that the enhanced expression of heme oxygenase-1 in monocytes plays a role in monocyte deactivation. (2) Polymorphonuclear leukocyte (PMNL) functions: The intranuclear expressions of NF-kB and glucocorticoid receptor in PMNLs were s … More ignificantly enhanced in SIRS patients. There was a strong correlation between these two transcriptional factors. The balance between expression of NF-kB and glucocorticoid receptors may regulate the PMNL activation and inflammatory response following severe insults. Activated PMNLs enhanced the production of microparticles with increased adhesion molecules to endothelium. On the other hand, activated PMNLs enhanced the secretion of hepatocyte growth factor, which supports the significant role of PMNLs in tissue repair following severe insults. (3) Vascular endothelial functions : Endothelium-derived microparticles in circulating blood were significantly increased in patients with severe SIRS, and the binding of microparticles to the activated PMNLs was enhanced. These results showed that the interaction between PMNLs and emdothelium may play an important role in inflammatory response following severe insults. (4) Gamma-delta T-cell functions : Gamma-delta T-cells were significantly activated and decreased in the circulating blood in patients with severe SIRS. Gamma-delta T-cells may play a key role in host innate immunity following severe insults. Less