Effects of Interleukin-1α and Cyclosporin A in vivo and in vitro on Bone and Lymphoid Tissues in Mice

The purpose of this study was to investigate the effects of interleukin-1α (IL-1α) infusion and the ability of cyclosporin A (CYA) to alter IL-1α-induced effects on bone in vivo and in vitro and lymphoid organs in vivo. Mice were administered: IL-1α (2,4, or 6 days), CYA (6 days), or IL-1α and CYA (6 days). Hypercalcemia was induced in mice treated with IL-1α compared to controls and CYA treated mice, and decreased urinary calcium excretion was present in IL-1α 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-1α. Although CYA-treatment increased bone formation as compared to IL-1α-treatment; CYA in combination with IL-1α did not alter the reduction in mineral apposition rate caused by IL-1α. IL-1α also stimulated bone resorption in vitro which was significantly inhibited by cyclosporin A. IL-1α-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-1α was effective in stimulating hypercalcemia and bone resorption both in vivo and in vitro but cyclosporin A was effective in inhibiting IL-1α -mediated bone resorption only in vitro. IL-1α also had marked effects on spleen, thymus, and circulating blood cells; however, most parameters were not affected by the concurrent administration of cyclosporin A.