INCREASE IN CYTOKINE PRODUCTION (IL-1-BETA, IL-6, TNF-ALPHA BUT NOT IFN-GAMMA, GM-CSF OR LIF) BY STIMULATED WHOLE-BLOOD CELLS IN POSTMENOPAUSAL OSTEOPOROSIS

Postmenopausal osteoporosis is a progressive disorder characterized by a decreased bone mass and increased susceptibility to fractures. Seve ral investigations have suggested that ne of the mechanisms through wh ich estrogen prevents bone loss was a modulation on secretion or relea se of Various cytokines that are known to influence bone remodeling, e ven if some recent data have challenged this hypothesis. However, in e stablished osteoporosis, the possibility that enhanced cytokines activ ity may account for the progression of this disease remains unclear an d controversial. We sought here to determine whether production of IL- 1 beta, IL-6, TNF-alpha, IFN-gamma, GM-CSF and LIF, after direct stimu lation in whole blood, was different in healthy (n = 30) or osteoporot ic postmenopausal women (n = 24) and whether lumbar bone density (1-BM D) correlated with the Values of cytokine production observed in these conditions. A significant difference was observed between the osteopo rotic and control subjects for IL-IP (p < 0.0001), IL-6 (p < 0.001) an d TNF-alpha (p = 0.027) productions, the values being higher in the os teoporotic women. No significant differences between the groups were o bserved for IFN-gamma (p = 0.51), GM-CSF (p = 0.70) or LIF (p = 0.97). In the whole population, statistically significant negative correlati ons were observed between lumbar BMD and IL-1 beta (r = -0.46) (p < 0. 0005), IL-6 (r = -0.50) (p < 0.0001) and TNF-alpha (r = -0.39) (p < 0. 005) production while no such correlations were observed for IFN-gamma , GM-CSF or LIF. In conclusion, the study of cytokine production by im mune cells cultured in autologous whole blood suggests that in women m ore than 10 years past the menopause and presenting a decrease in lumb ar bone density corresponding to the new WHO definition of 'osteoporos is', production of IL-1 beta, IL-6 and TNF-alpha is still increased co mpared to controls matched for age and ovarian function, while no diff erences are reported for IFN-gamma, GM-CSF or LIF production. Copyrigh t (C) 1997 Elsevier Science Ireland Ltd.