Significance of Blood TNF-alpha and Interleukin 10 Levels in Vibrio Vulnificus Cytolysin Toxemia

Chun, Jae Hoon; Cha, Seung Hoon; Park, Seok Don

Abstract

BACKGROUND: Pro-inflammatory cytokines, such as tumor necrosis factor(TNF)-alpha and interleukin (IL)-1, have been incriminated in the pathogenesis of septic shock in animals and humans. IL-10 reduces the release of pro-inflammatory cytokines, nitric oxide and reactive oxygen species. IL-10 prevents endotoxin-induced toxicity.
OBJECTIVE
The aim of this study was to investigate the relation between IL-10 and TNF-alpha in toxemic mice according to concentrations of V. vulnificus cytolysin.
METHODS
First, after administration of V.vulnificus cytolysin(2, 4, 6, 8, 10 hemolytic units; HU) and physiologic saline through a mouse tail vein, we obtained blood samples from the heart at 60 minutes which was a peak time of IL-10 and TNF-alpha release. We measured serum concentration of circulating TNF-alpha and IL-10 using commercially available enzyme-linked immunosorbent assay methods. Second, after administration of 1,000U recombinant mouse IL-10 through a mouse tail vein 30 min before infusion of the lethal dose(8HU) of V. vulnificus cytolysin. We obtained blood samples from the heart at 60 minutes and measured serum concentration of circulating TNF-alpha level.
RESULTS
Both IL-10 and TNF-alpha levels were significantly correlated with V. vulnificus cytolysin concentration(P=0.002). TNF-alpha levels were 76.9+/-9.5 pg/ml in 2HU, 315.8+/-39.8 pg/ml in 4HU, 426.1+/-27.9 pg/ml in 6HU, 931.3+/-22.3 pg/ml in 8HU, 1825.2+/-18.8 pg/ml in 10HU and 23.6+/-5.1 pg/ml in physiologic saline. IL-10 levels were 80.2+/-21.5 pg/ml in 2HU, 244.4+/-35.4 pg/ml in 4HU, 382.2+/-22.6 pg/ml in 6HU, 740.1+/-33.0 pg/ml in 8HU, 997.3+/-16.8 pg/ml in 10HU and 35.8+/-15.0 pg/ml in physiologic saline. After administration of 1,000U recombinant mouse IL-10, comparing to control group(931.3+/-22.3 pg/ml), TNF-alpha level was reduced to 307.2+/-23.9 pg/ml(P=0.003).
CONCLUSION
IL-10 has an inhibitory effect on the production of TNF-alpha although it is released together with TNF-alpha in toxemic mice. IL-10 blood levels are directly related to the severity of toxemia. We conclude that IL-10 is a prognostic factor for the development of sepsis and might be used for the treatment of sepsis.