Wiik P, Skrede K K, Knardahl S, Haugen A H, Aerø C E, Opstad P K, Bøyum A
Norwegian Defence Research Establishment, Division for Environmental Toxicology, Kjeller.
Acta Physiol Scand. 1995 Jul;154(3):407-16. doi: 10.1111/j.1748-1716.1995.tb09924.x.
Adrenoglucocorticoid regulation of rat peritoneal monocyte/macrophage function was studied by exposing rats to corticosterone (CS) in the drinking water, and to fast (48 h). Production of reactive oxygen metabolites was measured by luminol amplified chemiluminescence (CL) in preparations of peritoneal cells activated by serum treated zymosan (STZ). Administration of CS which led to an increase in plasma CS from 31 (controls) to 46 ng mL-1, reduced CL (per cell) by 31%. Fast, which did not change plasma CS or ACTH, also had an inhibitory effect on CL (-25%), while the combination of CS administration and fast strongly inhibited the CL (-89%), indicating that plasma CS and fast reduced CL in a synergistic way. Similar effects on cell number were observed: CS-administration, fast and the combination reduced macrophage numbers (-13, -19.7 and -55%), while no significant effect was observed on the number of monocytes. The effect of adrenalectomy (adx) was studied in another series of experiments; adx induced no significant change in peritoneal leucocyte number or composition, while cells from adx animals had significantly higher chemiluminescence reaction than cells from sham operated animals. CS substitution in adx animals reduced CL by 30% while sham operated animals had 49% lower CL in adx. The data from adx animals also suggest that endogenous levels of CS are inhibitory for CL, but the results are not conclusive for the effect of very low doses of CS since other mechanisms than elimination of CS could prime the chemiluminescence reaction after adx. In conclusion, a moderate elevation of CS after systemic administration in vivo reduced the total number of mononuclear phagocytes in rat peritoneum, reduced the relative number of macrophages compared with monocytes, and suppressed the function of monocytes/macrophages by reducing the production of reactive oxygen molecules in activated cells. Furthermore, the effect of corticosterone was also dependent on the physiological situation, since the effects of fast and corticosterone were synergistic.
通过让大鼠饮用含皮质酮(CS)的水并禁食(48小时),研究了肾上腺糖皮质激素对大鼠腹膜单核细胞/巨噬细胞功能的调节作用。通过鲁米诺增强化学发光(CL)法测定经血清处理的酵母聚糖(STZ)激活的腹膜细胞制剂中产生活性氧代谢产物的情况。给予CS后,血浆CS从31(对照组)增加到46 ng/mL,使CL(每细胞)降低了31%。禁食虽未改变血浆CS或促肾上腺皮质激素(ACTH)水平,但对CL也有抑制作用(-25%),而给予CS与禁食相结合则强烈抑制CL(-89%),这表明血浆CS和禁食以协同方式降低CL。在细胞数量上观察到类似的效应:给予CS、禁食以及二者结合均减少了巨噬细胞数量(分别为-13%、-19.7%和-55%),而对单核细胞数量无显著影响。在另一系列实验中研究了肾上腺切除术(adx)的作用;adx对腹膜白细胞数量或组成无显著影响,而来自adx动物的细胞比假手术动物的细胞具有显著更高的化学发光反应。在adx动物中给予CS替代物使CL降低30%,而假手术动物在adx情况下CL降低49%。来自adx动物的数据还表明内源性CS水平对CL有抑制作用,但由于除了去除CS之外的其他机制可能在adx后引发化学发光反应,所以对于极低剂量CS的作用结果并不确凿。总之,体内全身给药后CS的适度升高减少了大鼠腹膜中单核吞噬细胞的总数,降低了巨噬细胞相对于单核细胞的相对数量,并通过减少活化细胞中产生活性氧分子来抑制单核细胞/巨噬细胞的功能。此外,皮质酮的作用还取决于生理状态,因为禁食和皮质酮的作用是协同的。