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.


METHODS
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.
Vukicević
S
S
Department of Anatomy Biochemistry, School of Medicine, University of Zagreb, Croatia.
Marusić
A
A
Stavljenić
A
A
Cesnjaj
M
M
Ivanković
D
D
D000210:Acute-Phase Reaction / Q000209:etiology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D001862:Bone Resorption / Q000209:etiology*; D002097:C-Reactive Protein / Q000032:analysis; D003300:Copper / Q000097:blood; D005260:Female; D015745:Granuloma, Foreign-Body / Q000150:complications* / Q000209:etiology; D006965:Hyperplasia; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology; D007501:Iron / Q000097:blood; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013627:Talc / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*; D015430:Weight Gain; D015032:Zinc / Q000097:blood
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D013627:Talc; D003300:Copper; D000324:Adrenocorticotropic Hormone; D002097:C-Reactive Protein; D007501:Iron; D015032:Zinc