Effect of surgical menopause and estrogen replacement on cytokine release from human blood mononuclear cells.

TLDR

The study aimed to determine whether mononuclear cell secretory products contribute to bone turnover changes seen in postmenopausal osteoporosis by evaluating the effects of oophorectomy and estrogen replacement on IL‑1, TNF‑α, and GM‑CSF secretion. Cytokine secretion was measured in peripheral blood mononuclear cells from 15 premenopausal women before and after oophorectomy, with or without estrogen replacement, assessing spontaneous IL‑1, TNF‑α, and GM‑CSF release and PHA‑induced GM‑CSF production. After oophorectomy, GM‑CSF rose within a week, while IL‑1, TNF‑α, and bone‑resorption markers increased after two weeks; in women without estrogen therapy these markers peaked at eight weeks, whereas estrogen replacement begun four weeks post‑surgery lowered cytokine levels and bone‑resorption indices within two weeks, with no changes observed in hysterectomy controls.

Abstract

To determine whether mononuclear cell secretory products contribute to the changes in bone turnover that characterize the development of postmenopausal osteoporosis, we evaluated the effects of oophorectomy and subsequent estrogen replacement on the spontaneous secretion of interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) and on the phytohemagglutinin A-induced secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) from peripheral blood mononuclear cells. In 15 healthy premenopausal women who underwent oophorectomy, increases in GM-CSF activity were observed as early as 1 week after surgery, whereas elevations in IL-1 and TNF-alpha and in hydroxyproline/creatinine and calcium/creatinine ratios, two urinary indices of bone resorption, were detectable 2 weeks after the surgical procedure. Six of the oophorectomized women received no estrogen therapy after surgery and in these subjects hydroxyproline/creatinine and calcium/creatinine ratios plateaued 6 weeks postoperatively, and all three cytokines reached the highest levels 8 weeks after oophorectomy, when the study ended. In the remaining 9 women, who were started on estrogen replacement therapy 4 weeks after oophorectomy, decreases in the indices of bone resorption paralleled decreases in the secretion of the cytokines, with lower levels detected after 2 weeks of therapy. In the women who did not receive estrogen therapy, circulating osteocalcin, a marker of bone formation, increased beyond preoperative levels 8 weeks after oophorectomy, whereas in the estrogen-treated subjects osteocalcin remained unchanged in the entire study period. In 9 female controls who underwent simple hysterectomy, cytokine release and biochemical indices of bone turnover did not change after surgery. These data indicate that changes in estrogen status in vivo are associated with the secretion of mononuclear cell immune factors in vitro and suggest that alterations in the local production of bone-acting cytokines may underlie changes in bone turnover caused by surgically induced menopause and estrogen replacement.