THE ROLE OF TUMOR-NECROSIS-FACTOR-ALPHA IN THE GENERATION OF ACUTE-PHASE RESPONSE AND BONE LOSS IN RATS WITH TALC GRANULOMATOSIS

BACKGROUND: Trabecular bone loss is the part of acute-phase response ( APR) in rats with subcutaneous granulomatous inflammation induced by t alc. 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 ad ministration of specific neutralizing antibodies to TNF-alpha or of re combinant cytokine indicated that TNF-alpha was the primary mediator o f bone changes, evidenced as slower bone elongation rate, bone marrow hyperplasia, and decreased trabecular bone volume and osteoblast numbe r in tibial metaphysis. RESULTS: Moreover, direct intraosseal administ ration of anti-TNF-a antibody neutralized the effect of inflammation o n bone. On the other hand, the serum indices of the APR (decreased zin c and iron concentrations, ACTH and C-reactive protein concentration) were not greatly affected after the administration of anti-TNF antibod y, except for the normalization of the hypercupremia and weight loss. CONCLUSIONS: The data presented in this report demonstrated direct inv olvement of TNF-alpha in the generation of bone alterations during the development of APR in rats with talc granulomatosis.