Effect of immune cytokines on bone.
The effect of the bone resorptive cytokines IL-1 alpha, IL-1 beta, and TNF on bone formation was studied in an in vitro system. All three cytokines were profoundly inhibitory, with the rank order of potency IL-1 beta greater than IL-1 alpha greater than TNF. Inhibition was mediated by a depression of differentiated osteoblast functions, including alkaline phosphatase expression and matrix synthesis. Osteoblast proliferation was not affected. Bone formation inhibition was independent of PGE2 production, indicating a direct effect of cytokines on osteoblasts. High concentrations of IL-1 beta (10 U/ml) abrogated IGF-1-stimulated bone formation, providing evidence for the hypothesis that cytokines act as 'uncoupling factors'. Conversely, high concentrations of IGF-1 circumvented inhibition by IL-1 beta (0.1-1.0 U/ml). The interaction of cytokines and bone growth factors with osteoblasts are likely to be of critical importance in the regulation of bone mass at local inflammatory sites.
Stashenko
P
P
Department of Immunology, Forsyth Dental Center, Boston, MA.
Obernesser
M S
MS
Dewhirst
F E
FE
D000818:Animals; D001685:Biological Factors / Q000494:pharmacology*; D001862:Bone Resorption / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects*; D016207:Cytokines; D015232:Dinoprostone / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D001685:Biological Factors; D016207:Cytokines; D006133:Growth Substances; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone