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Interleukin‐6 messenger RNA expression and interleukin‐6 protein secretion in cells isolated from normal human bone: Regulation by interleukin‐1

Recent evidence suggests that cytokines, in addition to regulating hematopoiesis and immune functions, may be important paracrine regulators of bone turnover. Interleukin‐1 (IL‐1) and IL‐6 are cytokines that are produced by and affect both hematopoietic and nonhematopoietic cell types. IL‐1 stimulates bone resorption and inhibits osteoblast proliferation and collagen production. Previous reports that IL‐6 was secreted in murine osteoblast and bone organ cultures in response to IL‐1 and PTH suggested that IL‐6 has paracrine effects on bone resorption or formation. To determine whether IL‐6 has a paracrine function in human bone, IL‐6 expression in cells isolated from normal human bone was investigated. IL‐6 mRNA levels in untreated cultures were low and variable, and IL‐6 secretion was undetectable. PTH had no effect on IL‐6 mRNA levels or IL‐6 secretion. IL‐1β increased IL‐6 mRNA levels, maximally 40‐fold at 12 h. IL‐1β increased IL‐6 secretion to 0.13 nM, more than 80‐fold that of untreated controls at 12 h. IL‐1β also increased IL‐1β mRNA levels, maximally 9‐fold at 12 h, but did not increase cellular levels or secretion of IL‐1β protein. Recombinant human IL‐6 at 0.5–5 nM stimulated resorption in neonatal mouse calvarial organ cultures but had no effect on human bone‐derived cell DNA synthesis or type I procollagen mRNA levels. The results suggest that IL‐6 production by human osteoblasts may function to enhance osteolytic activity of IL‐1 but does not affect proliferative and matrix biosynthetic aspects of bone formation that were tested. Because osteoblasts and bone marrow cells are in close proximity, IL‐6 produced by osteoblasts may also function to amplify IL‐1 stimulation of immune responses and hematopoiesis in bone marrow.