McCauley L K, Rosol T J, Stromberg P C, Capen C C
Department of Veterinary Pathobiology, Ohio State University, Columbus 43210.
Toxicol Pathol. 1991;19(1):1-10. doi: 10.1177/019262339101900101.
The purpose of this study was to investigate the effects of interleukin-1 alpha (IL-1 alpha) infusion and the ability of cyclosporin A (CYA) to alter IL-1 alpha-induced effects on bone in vivo and in vitro and lymphoid organs in vivo. Mice were administered: IL-1 alpha (2, 4, or 6 days), CYA (6 days), or IL-1 alpha and CYA (6 days). Hypercalcemia was induced in mice treated with IL-1 alpha compared to controls and CYA treated mice, and decreased urinary calcium excretion was present in IL-1 alpha and CYA groups. Osteoclastic bone resorption was increased with a resultant loss of total bone area and bone formation (as measured by mineral apposition rate) was decreased in mice infused with IL-1 alpha. Although CYA-treatment increased bone formation as compared to IL-1 alpha-treatment; CYA in combination with IL-1 alpha did not alter the reduction in mineral apposition rate caused by IL-1 alpha, IL-1 alpha also stimulated bone resorption in vitro which was significantly inhibited by cyclosporin A. IL-1 alpha-induced splenic granulopoiesis, peripheral blood neutrophilia, thymic atrophy, and lymphoid hyperplasia in lymph nodes. CYA-treatment resulted histologically in a severe depletion of lymphocytes in the thymus, a moderate depletion of lymphocytes in lymph nodes but no difference in the histology of the spleen compared to controls. In summary, interleukin-1 alpha was effective in stimulating hypercalcemia and bone resorption both in vivo and in vitro but cyclosporin A was effective in inhibiting IL-1 alpha-mediated bone resorption only in vitro. IL-1 alpha also had marked effects on spleen, thymus, and circulating blood cells; however, most parameters were not affected by the concurrent administration of cyclosporin A.
本研究的目的是调查白细胞介素 -1α（IL-1α）输注的影响以及环孢素A（CYA）改变IL-1α在体内和体外对骨骼以及在体内对淋巴器官所诱导效应的能力。给小鼠施用：IL-1α（2、4或6天）、CYA（6天）或IL-1α与CYA（6天）。与对照组和接受CYA治疗的小鼠相比，接受IL-1α治疗的小鼠出现高钙血症，并且IL-1α组和CYA组的尿钙排泄减少。在输注IL-1α的小鼠中，破骨细胞性骨吸收增加，导致总骨面积减少，骨形成（通过矿物质沉积率测量）降低。尽管与IL-1α治疗相比，CYA治疗增加了骨形成；但CYA与IL-1α联合使用并未改变IL-1α引起的矿物质沉积率降低，IL-1α在体外也刺激了骨吸收，而环孢素A可显著抑制这种作用。IL-1α诱导脾脏粒细胞生成、外周血中性粒细胞增多、胸腺萎缩以及淋巴结淋巴样增生。CYA治疗在组织学上导致胸腺中淋巴细胞严重耗竭，淋巴结中淋巴细胞中度耗竭，但与对照组相比，脾脏组织学无差异。总之，白细胞介素 -1α在体内和体外均能有效刺激高钙血症和骨吸收，但环孢素A仅在体外能有效抑制IL-1α介导的骨吸收。IL-1α对脾脏、胸腺和循环血细胞也有显著影响；然而，大多数参数不受同时施用环孢素A的影响。
