Abstract
Bone marrow fibrosis occurs in association with a number of pathological states. Despite the extensive fibrosis that sometimes characterizes renal osteodystrophy, little is known about the factors that contribute to marrow accumulation of fibrous tissue. Because circulating cytokines are elevated in uremia, possibly in response to elevated parathyroid hormone levels, we have examined bone biopsies from 21 patients with end-stage renal disease and secondary hyperparathyroidism. Bone sections were stained with antibodies to human interleukin-1alpha (IL-1alpha), IL-6, IL-11, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta) using an undecalcified plastic embedding method. Intense staining for IL-1alpha, IL-6, TNF-alpha and TGF-beta was evident within the fibrotic tissue of the bone marrow while minimal IL-11 was detected. The extent of cytokine deposition corresponded to the severity of fibrosis, suggesting their possible involvement in the local regulation of the fibrotic response. Because immunoreactive TGF-beta and IL-6 were also detected in osteoblasts and osteocytes, we conclude that selective cytokine accumulation may have a role in modulating bone and marrow cell function in parathyroid-mediated uremic bone disease.
Highlights
Bone marrow fibrosis occurs in pathological states that characterize idiopathic myelofibrosis [1,2] and hyperparathyroid bone disease [3,4]
Because circulating cytokines are elevated in uremia, possibly in response to elevated parathyroid hormone levels, we have examined bone biopsies from 21 patients with end-stage renal disease and secondary hyperparathyroidism
We have shown that the bone marrow space of patients with secondary hyperparathyroidism shows significant accumulations of IL-1a, IL-6, tumor necrosis factor-a (TNF-a) and transforming growth factor-ß (TGF-ß) within discrete areas of fibrosis
Summary
Bone marrow fibrosis occurs in pathological states that characterize idiopathic myelofibrosis [1,2] and hyperparathyroid bone disease [3,4]. As seen from studies of idiopathic myelofibrosis, growth factors and cytokines are believed to promote a marrow proliferative response and the accumulation of extracellular matrix proteins [2]. Whether these factors are implicated in uremic bone disease is unknown. Cytokines and locally derived growth factors have important roles in regulating normal bone metabolism [8,9] and circulating levels of specific cytokines are elevated in renal failure [10,11]. The finding that PTH can stimulate selective cytokine synthesis [13] suggests that the hyperparathyroidism of renal failure may be a significant stimulus for cytokine accumulation in renal osteodystrophy
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