Takao T, Nagano I, Tojo C, Takemura T, Makino S, Hashimoto K, De Souza E B
Second Department of Internal Medicine, Kochi Medical School, Nankoku, Japan.
Neuroimmunomodulation. 1996 Jul-Aug;3(4):205-12. doi: 10.1159/000097272.
The cytokine interleukin-1 (IL-1) alters a variety of immune, central nervous system and neuroendocrine activities characteristic of an integrator of the brain-endocrine-immune response to stress. In an attempt to define the regulation of IL-1 and IL-1 receptors in the mouse brain-endocrine-immune axis during maturation, we measured tissue levels of IL-1beta using an ELISA and iodine-125-labeled recombinant human interleukin-1alpha ([125I]IL-1alpha) binding in hippocampus, pituitary, testis and spleen following intraperitoneal injection of saline or the bacterial endotoxin, lipopolysaccharide (LPS) in 3- and 24-week-old C57BL/6 mice. Basal IL-1beta levels were detectable in all the tissues examined. Basal levels of IL-1beta in the hippocampus, spleen and testis in 24-week-old mice were significantly higher than those in 3-week-old mice. [125I]IL-1alpha binding was detectable in all the mouse tissues examined and [125I]IL-1alpha binding levels in the pituitary, spleen and testis in 3-week-old mice were significantly higher than those in 24-week-old mice. To further evaluate the modulation of IL-1 receptors in aging, we measured [125I]IL-1alpha binding in 2-, 5-, 10-, 18-, and 24-month-old mice. [125I]IL-1alpha binding in testis in 24-month-old mice was higher than the other groups; [125I]IL-1alpha binding in the hippocampus and spleen was unchanged during these periods. Dramatic increases in IL-1beta concentrations were observed at 2 h after LPS injection in the pituitary, spleen, testis and plasma in both 3- and 24-week-old mice groups. In contrast, IL-1beta levels in the hippocampus increased in response to LPS injection only in 24-week-old mice. [125I]IL-1alpha binding in hippocampus was significantly decreased in 24- but not in 3-week-old mice after LPS injection. [125I]IL-1alpha binding in the spleen and testis were significantly decreased in both age groups following LPS administration. These data demonstrate differential regulation of IL-1 and its receptors in the brain-endocrine-immune axis during maturation and in response to endotoxin challenge.
细胞因子白细胞介素-1（IL-1）可改变多种免疫、中枢神经系统及神经内分泌活动，这些活动是大脑-内分泌-免疫对应激反应的整合特征。为了确定在成熟过程中小鼠脑-内分泌-免疫轴中IL-1及其受体的调节情况，我们在3周龄和24周龄的C57BL/6小鼠腹腔注射生理盐水或细菌内毒素脂多糖（LPS）后，使用酶联免疫吸附测定（ELISA）和碘-125标记的重组人白细胞介素-1α（[125I]IL-1α）结合法，测量了海马、垂体、睾丸和脾脏中IL-1β的组织水平。在所检测的所有组织中均可检测到基础IL-1β水平。24周龄小鼠海马、脾脏和睾丸中的基础IL-1β水平显著高于3周龄小鼠。在所检测的所有小鼠组织中均可检测到[125I]IL-1α结合，且3周龄小鼠垂体、脾脏和睾丸中的[125I]IL-1α结合水平显著高于24周龄小鼠。为了进一步评估衰老过程中IL-1受体的调节情况，我们测量了2、5、10、18和24月龄小鼠的[125I]IL-1α结合。24月龄小鼠睾丸中的[125I]IL-1α结合高于其他组；在此期间，海马和脾脏中的[125I]IL-1α结合未发生变化。在3周龄和24周龄小鼠组中，垂体、脾脏、睾丸和血浆在LPS注射后2小时均观察到IL-1β浓度急剧升高。相比之下，仅在24周龄小鼠中，海马中的IL-1β水平在LPS注射后升高。LPS注射后，24周龄小鼠海马中的[125I]IL-1α结合显著降低，而3周龄小鼠则未降低。LPS给药后，两个年龄组脾脏和睾丸中的[125I]IL-1α结合均显著降低。这些数据表明，在成熟过程中以及对内毒素刺激的反应中，脑-内分泌-免疫轴中IL-1及其受体存在差异调节。
