Effects of interleukin-1 alpha 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-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.
McCauley
L K
LK
Department of Veterinary Pathobiology, Ohio State University, Columbus 43210.
Rosol
T J
TJ
Stromberg
P C
PC
Capen
C C
CC
D000818:Animals; D001772:Blood Cell Count / Q000187:drug effects; D001862:Bone Resorption / Q000139:chemically induced; D001842:Bone and Bones / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D003524:Cyclosporins / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology*; D008221:Lymphoid Tissue / Q000187:drug effects*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D012867:Skin / Q000187:drug effects
D003524:Cyclosporins; D007375:Interleukin-1; D002118:Calcium