Bone-resorbing cytokines from peripheral blood mononuclear cells after hormone replacement therapy: A longitudinal study

Conflicting results have been reported in several cross-sectional studies m easuring cytokine production from adherent monocytes in pre- and postmenopa usal women. Furthermore, the target cells for the action of estrogen are st ill debated. We therefore assessed in a longitudinal manner the cytokine pr oduction from different fractions of peripheral blood mononuclear cells (PB MC) cultured for 48 h. PBMC were obtained from 30 postmenopausal women befo re and after 6 months of hormone replacement therapy (HRT). Women were rand omly allocated to two groups: an adherent PBMC group (n = 20) and a total P BMC group (n = 9). After 6 months of treatment, urinary pyridinoline levels were markedly decreased in both groups (353 +/- 24 vs 114 +/- 13 mug/mmol creatinine and 325 +/- 35 vs 164 +/- 31 mug/mmol creatinine respectively, p <0.01). Culture supernatants were assayed for interleukin 1 beta (IL-1 bet a), interleukin 6 (IL-6), soluble IL-6 receptor (IL-6rs) and tumor necrosis factor alpha (TNF-alpha). In the adherent PBMC group, HRT induced a nonsig nificant trend toward decreased levels of IL-1 beta (35 +/- 10 vs 13 +/- 5 pg/ml), TNF-alpha (333 +/- 58 vs 222 +/- 30 pg/ml) and IL-6 (115 +/- 70 vs 17 +/- 10 pg/ml). In contrast, in the total PBMC group, HRT induced a consi stent and dramatic decrease in levels of IL-1 beta (104 +/- 22 vs 25 +/- 8 pg/ml), IL-6 (5950 +/- 1041 vs 1011 +/- 361 pg/ml), IL-6rs (148 +/- 33 vs 3 5 +/- 12 pg/ml) (p <0.01) and TNF-alpha (1468 +/- 315 vs 585 +/- 207 pg/ml, p = 0.05). We then evaluated whether HRT had the same effect in vitro. Adh erent or total PBMC of 8 postmenopausal women were cultured with or without 10(-8)M 17 beta -estradiol or tibolone for 48 h. Production of IL- 1 beta, TNF-alpha, IL-6 and IL-6rs was not affected by the presence of 17 beta -es tradiol or tibolone in cultures of these cell fractions. In conclusion, our data indicate that non-adherent PBMC could mediate the response to HRT. HR T may exert its action indirectly via noncirculating cells, as suggested by the absence of an in vitro effect.