FUNCTIONAL MODIFICATION OF VASCULAR ENDOTHELIAL-CELLS BY CYTOKINES DURING SEPTIC SHOCK

The function of vascular endothelial cells is to adjust blood vessel t onus, which contributes to maintaining homeostasis within blood vessel s. However, inflammatory cytokines are produced in response to invasio n by stimulating vascular endothelial cells and sometimes lead to shoc k or multiple organ failure. In the present study, we assessed cytokin es in sepsis and septic shock, and various factors that are said to ha ve a damaging effect on vascular endothelium. Endotoxin was measured b y endotoxin-specific methods. Tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and interleukin 8 (IL-8) were measured by enzym e-linked immunosorbent assay (ELISA). Endothelin-1 was measured by rad ioimmunoassay (RIA). Nitric oxide was measured as metabolites of nitri te and nitrate oxides (NOx) by a method based on the Griess method. Th romboxane B-2 (TXB(2)) and 6-keto-prostaglandin F-1 alpha (PGF(1 alpha )) were both measured by RIA. All of the factors except endotoxin were significantly higher in the septic shock group than in the non-shock group and significantly higher in the non-survivor group than in the s urvivor group. Significant correlations were also found between endoth elin-1 and NOx and between TXB(2) and PG(1 alpha). Significant correla tions were also found between TNF-alpha and IL-6, endothelin-1, NOx an d TXB(2), but no significant correlations were detected between any of them and endotoxin. In serious diseases such as septic shock, the vas cular endothelial constricting factors, endothelin and TXB(2), and the blood vessel relaxing factors NOx and PGF(1 alpha) increase almost si multaneously. This suggests that the body's regulating mechanisms are disrupted in these serious conditions. The results of this study also suggest that inflammatory cytokines may be involved in stimulating the production of these factors.