| Co-Investigator(Kenkyū-buntansha) |
INOUE Kinji Saitama University, Dept of Cell Biology, Professor, 理学部, 教授 (50091963)
FUJIMIYA Mineko Shiga Medical School, Dept of Anatomy, Associated Professor, 医学部, 助教授 (10199359)
SUDO Nobuyuki Kyushu University, Dept. of Physiology, Assistant Professor, 大学院・医学研究院, 助手 (60304812)
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| Research Abstract |
It has long been known that plasma intereukin (IL)-6 levels elevate during non inflammatory, physico/ psychological stresses such as immobiliztion (1MB) and electric foot shock. (FS) We previously demonstrated that an IMB-induced rise in plasma IL-6 in the rat was caused, at least partly, by an increased production of IL-6 in hepatic reticuloendothelial cells which were induced by enteric flora derived lipopolysccharide (LPS). This study investigated whether such enteric flora-derived LPS may produce IL-6 also in the mesentery and the mesenteric lymphoid nodes (MLN) before it reaches the liver. We found a rise in the IL-6 levels in the hepato- portal vein (PV) within 30 min during FS, while the IL-6 levels in thejugular vein showed a smaller and delayed rise with slower recovery. Plasma IL-6 levels near the exit of the hepatic vein in the inferior vena cava was highest at both control and stressed conditions, compared with those in the PV and any other extra-hepatic circulation. The stress-induced IL-6 elevation in the PV was abolished by an in vivo neutralization of LPS with continuous infusion of polymyxin B. Furthermore, the amount of LPS as assessed by its bioactivity increased rapidly in the mesentery, the MLN and the liver within 15 min after the start of FS. Finally, fluorescent dye-labeled LPS infused into the lumen of the ileum was found in the extraintestinal tissues and systemic vein, and FS increased the optical density. The findings suggest that these lymphoid organs are continuously exposed to LPS at the basal condition and FS facilitates the LPS/bacterial translocation across the intestinal wall and thereby increases the production of IL-6 in the gut associated lymphoid organs before LPS reaches the liver.
In addition to this, we claryfied the roles of LPS on pituitary cells, DNA oxidative damages, etc, in this project. We can summarize the LPS act as a key mediator to establish and keep the host-defense mechanism like an intrinsic humoral factor.
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