Role of several mediators of inflammation on the mouse hypothalamo-pituitary-adrenal axis response during acute endotoxemia
Role of several mediators of inflammation on the mouse hypothalamo-pituitary-adrenal axis response during acute endotoxemia
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DOI：
10.1159/000026393
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发表时间：
1999-09-01
影响因子：
2.4
通讯作者：
Gaillard, RC
中科院分区：
文献类型：
--
作者：
Hadid, R;Spinedi, E;Gaillard, RC
细菌内毒素激活的免疫细胞分泌的细胞因子是已知刺激下丘脑-垂体-肾上腺（HPA）轴功能的物质。本研究旨在更好地了解不同炎症介质（如细胞因子和组胺）对成年雄性BALB/c小鼠单剂量细菌脂多糖（LPS）诱导的急性HPA轴反应的影响。设置了两种不同的实验设计。在第一个设计中，小鼠（每组8-11只）腹腔注射LPS （90 μ g/kg体重），在给药2或6 h后斩首处死。另一组小鼠在LPS治疗前12小时预处理：(a)抗肿瘤坏死因子- α (TNF)- α、抗白细胞介素(IL)-1 β -或IL-6血清3-4 mg IgG/kg体重；(b) LPS处理前立即和3小时后（注射LPS 6小时后处死动物）的IL-1受体拮抗剂（IL-1ra） （120 μ g/kg体重），或(c) LPS处理前2小时h -1组胺能受体拮抗剂clemastine （182 μ g/kg体重）；动物被杀死的方式与单独使用LPS治疗的方式相似。在第二个实验设计中，用不同的组胺能通路阻滞剂预处理小鼠（剂量为10mg/kg体重，给药前30分钟给予类似剂量的LPS），这些阻滞剂包括：(a)另一种抗h -1药物甲胺，(b) Hp受体阻滞剂西咪替丁，以及(c) H-3突触前受体激动剂ra -甲基组胺二盐酸，一种抑制组胺合成和输出的H-3受体激动剂。内毒素处理40分钟后，将其斩首处死。砍头后采集干血，通过特异性测定进一步测定血浆ACTH和皮质酮(B)水平。结果表明，在给药后2和6小时，血浆ACTH和B水平比基线增加了数倍。2小时后，尽管IL-1ra处理能够完全阻断IL-1 β （35 μ g/kg体重）刺激的HPA轴功能，但抗IL-1 β IgG、抗il -6 IgG、抗tnf - α IgG或IL-1ra预处理均未改变LPS对ACTH输出的影响。细胞因子给药2h后。给药6小时后，抗il -1 β和抗tnf - α。
Cytokines secreted by bacterial endotoxin-activated immune cells are substances known to stimulate the hypothalamo-pituitary-adrenal (HPA) axis function. The present study was designed to better understand the effect of different mediators of inflammation, such as cytokines and histamine, on the acute HPA axis response induced by administration of a single dose of bacterial lipopolysaccharide (LPS) in adult, male, BALB/c mice. Two different experimental designs were set up. In the first design, mice (n = 8-11 per group) were injected i.p. with LPS (90 mu g/kg body weight) and killed by decapitation 2 or 6 h after treatment. Additional groups of mice were pretreated i.p. 12 h before LPS treatment with: (a) 3-4 mg IgG/kg body weight of either an anti-tumor necrosis factor-alpha (TNF)-alpha, anti-interleukin (IL)-1 beta- or IL-6 serum; (b) IL-1 receptor antagonist (IL-1ra) (120 mu g/kg body weight) immediately before LPS and also 3 h later (when animals were killed 6 h after LPS injection), or (c) 182 mu g/kg body weight of clemastine, an antagonist of H-1 histaminergic receptors, 2h before LPS treatment; animals were kilted in a similar fashion to that described for treatment with LPS alone. In the second experimental design, mice were pretreated (i.p., 10mg/kg body weight, 30 min before administration of a similar dose of LPS) with different blockers of histaminergic pathway function such as: (a) mepyramine, another anti-H-1, (b) cimetidine, an Hp receptor blocker, and (c) Ra-methylhistamine dihydrochloride, an H-3 presynaptic receptor agonist which inhibits histamine synthesis and output. These animals were then killed by decapitation 40 min after endotoxin treatment. After decapitation, trunk blood was collected for further determination of plasma levels of both ACTH and corticosterone (B) by specific assays. The results indicate that plasma levels of both ACTH and B were several-fold increased over baseline, 2 and 6 h after LPS administration. Two hours, the effect of LPS on ACTH output was not modified by pretreatment with anti-IL-1 beta IgG, anti-IL-6 IgG, anti-TNF-alpha IgG nor with IL-1ra, although IL-1ra treatment was able to fully block the IL-1 beta (35 mu g/kg body weight)-stimulated HPA axis function, 1. and 2h after cytokine administration. Six hours after LPS administration, anti-IL-1 beta and anti-TNF-alpha.