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 measuring cytokine production from adherent monocytes in pre- and postmenopausal women. Furthermore, the target cells for the action of estrogen are still debated. We therefore assessed in a longitudinal manner the cytokine production from different fractions of peripheral blood mononuclear cells (PBMC) cultured for 48 h. PBMC were obtained from 30 postmenopausal women before and after 6 months of hormone replacement therapy (HRT). Women were randomly allocated to two groups: an adherent PBMC group (n = 20) and a total PBMC group (n = 9). After 6 months of treatment, urinary pyridinoline levels were markedly decreased in both groups (353+/-24 vs 114+/-13 microg/mmol creatinine and 325+/-35 vs 164+/-31 microg/mmol creatinine respectively, p<0.01). Culture supernatants were assayed for interleukin 1beta (IL-1beta), 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 nonsignificant trend toward decreased levels of IL-1beta (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 consistent and dramatic decrease in levels of IL-1beta (104+/-22 vs 25+/-8 pg/ml), IL-6 (5950+/-1041 vs 1011+/-361 pg/ml), IL-6rs (148+/-33 vs 35+/-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. Adherent or total PBMC of 8 postmenopausal women were cultured with or without 10(-8) M 17beta-estradiol or tibolone for 48 h. Production of IL-1beta, TNF-alpha, IL-6 and IL-6rs was not affected by the presence of 17beta-estradiol or tibolone in cultures of these cell fractions. In conclusion, our data indicate that non-adherent PBMC could mediate the response to HRT. HRT may exert its action indirectly via noncirculating cells, as suggested by the absence of an in vitro effect.
Bernard-Poenaru
O
O
INSERM U349, Hopital Lariboisière, Paris, France.
Roux
C
C
Blanqué
R
R
Gardner
C
C
de Vemejoul
M C
MC
Cohen-Solal
M E
ME
D000368:Aged; D000596:Amino Acids / Q000652:urine; D001862:Bone Resorption / Q000188:drug therapy / Q000378:metabolism*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004958:Estradiol / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008137:Longitudinal Studies; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077563:Norethindrone Acetate
D000596:Amino Acids; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D004958:Estradiol; C015484:pyridinoline; D000077563:Norethindrone Acetate; D009640:Norethindrone