The role of tumor necrosis factor-alpha in the generation of acute phase response and bone loss in rats and talc granulomatosis.
BACKGROUND: Trabecular bone loss is the part of acute-phase response (APR) in rats with subcutaneous granulomatous inflammation induced by talc. EXPERIMENTAL DESIGN: We investigated the possible involvement of inflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of bone loss and other aspects of APR. Intraperitoneal administration of specific neutralizing antibodies to TNF-alpha or of recombinant cytokine indicated that TNF-alpha was the primary mediator of bone changes, evidence as slower bone elongation rate, bone marrow hyperplasia, and decreased trabecular bone volume and osteoblast number in tibial metaphysis. RESULTS: Moreover, direct intraosseal administration of anti-TNF-alpha antibody neutralized the effect of inflammation on bone. On the other hand, the serum indices of the APR (decreased zinc and iron concentrations, ACTH and C-reactive protein concentration) were not greatly affected after the administration of anti-TNF antibody, except for the normalization of the hypercupremia and weight loss. CONCLUSIONS: The data presented in this report demonstrated direct involvement of TNF-alpha in the generation of bone alterations during the development of APR in rats with talc granulomatosis.