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

Abstract

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.

Effects of Cyclosporin A on Alveolar Bone: An Experimental Study in the Rat

“…[19][20][21]30 However, observations of decreased bone resorption following CSA administration have also been reported. 31 In vitro studies suggest an inhibitory effect of CSA on bone resorption stimulated by parathyroid hormone, interleukin-1, prostaglandin E 2 , and 1,25 dihydroxyvitamin D. 17,18,32,33 In a recent study, CSA prevented development of experimental arthritis and associated bone mineral loss in oral doses of 5 to 10 mg/kg; however, a 30 mg/kg dose produced toxic skeletal demineralization. 34 Apparently, controversy relative to CSA effects on bone metabolism may be explained, at least in part, by the dosage.…”

“…Although effects of CSA on bone have been carefully examined, the exact mechanisms are still controversial and remain uncertain. [14][15][16][17][18][19][20][21][22][23][24][30][31][32][33] Following controlled administration of CSA in rats, we observed a distinct pattern of alveolar bone turnover including increased osteoclasia in periodontal sites and reduced bone formation in symphyseal sites which may not present in adult humans. Within limitations of the study, we suggest that CSA has a distinct effect on aveolar bone metabolism.…”

Cyclosporin‐Induced Gingival Overgrowth at the Newly Formed Edentulous Ridge in Rats: A Morphological and Histometric Evaluation

“…38 An inhibitory effect of CsA on bone resorption, stimulated by parathyroid hormone, interleukin-1, prostaglandin E 2 , and 1,25 dihydroxyvitamin D, has been reported in vitro. [39][40][41][42] In a study of CsA preventing experimental arthritis, the associated bone mineral loss was observed at the oral doses of 5 to 10 mg/kg, while a 30 mg/kg dose produced toxic skeletal demineralization. 43 The controversy relative to CsA effects on bone metabolism may be explained, at least in part, by the dosage.…”

Mediators of Periodontal Osseous Destruction and Remodeling: Principles and Implications for Diagnosis and Therapy

“…12,28 Pharmacologic agents that inhibit bone resorption include cyclosporin, at least in part associated with its antiinflammatory properties, and bisphosphonates, which also stimulate osteoclast apoptosis. 29,30 …”