EFFECT OF SURGICAL MENOPAUSE AND ESTROGEN REPLACEMENT ON CYTOKINE RELEASE FROM HUMAN BLOOD MONONUCLEAR-CELLS
EFFECT OF SURGICAL MENOPAUSE AND ESTROGEN REPLACEMENT ON CYTOKINE RELEASE FROM HUMAN BLOOD MONONUCLEAR-CELLS
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DOI：
10.1073/pnas.88.12.5134
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发表时间：
1991-06-01
影响因子：
11.1
通讯作者：
AVIOLI, LV
中科院分区：
文献类型：
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作者：
PACIFICI, R;BROWN, C;AVIOLI, LV
为了确定单核细胞分泌产物是否有助于绝经后骨质疏松症发展的骨转换变化，我们评估了卵巢切除术和随后的雌激素替代对白细胞介素1（IL-1）和肿瘤坏死因子-α自发分泌的影响，（TNF-α）和植物血凝素A诱导的粒细胞-巨噬细胞集落刺激因子（GM-CSF）从外周血单核细胞的分泌。在15名健康的绝经前妇女接受卵巢切除术，GM-CSF活性增加，观察到早在术后1周，而IL-1和TNF-α和羟脯氨酸/肌酐和钙/肌酐比值升高，两个尿指标骨吸收，可检测到手术后2周。6名卵巢切除的妇女在手术后没有接受雌激素治疗，这些受试者的羟脯氨酸/肌酐和钙/肌酐比值在手术后6周达到平台，所有三种细胞因子在卵巢切除术后8周达到最高水平，研究结束。其余9名妇女在卵巢切除术后4周开始接受雌激素替代治疗，骨吸收指数下降导致细胞因子分泌减少，治疗2周后检测到较低水平。在没有接受雌激素治疗的妇女中，循环骨钙素，骨形成的标志物，在卵巢切除术后8周增加超过术前水平，而在雌激素治疗的受试者中，骨钙素在整个研究期间保持不变。在9名接受简单子宫切除术的女性对照中，手术后细胞因子释放和骨转换生化指标没有变化。这些数据表明，体内雌激素状态的变化与体外单核细胞免疫因子的分泌有关，并表明骨作用细胞因子的局部产生的改变可能是手术诱导的绝经和雌激素替代引起的骨转换变化的基础。
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.