Orchiectomy Increases Bone Marrow Interleukin-6 Levels in Mice
Orchiectomy Increases Bone Marrow Interleukin-6 Levels in Mice
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DOI：
10.1007/s002239900421
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发表时间：
1998-03
影响因子：
4.2
通讯作者：
J. Zhang;T. Pugh;B. S. Stebler;W. Ershler;Evan Keller
中科院分区：
文献类型：
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作者：
J. Zhang;T. Pugh;B. S. Stebler;W. Ershler;Evan Keller
白细胞介素-6（IL-6）似乎是与骨吸收相关的疾病状态中的重要因素。体外和体内证据都支持雄激素下调白细胞介素-6的产生。这些观察结果，结合成骨细胞和骨髓基质细胞产生IL-6的事实，使我们假设睾丸切除术诱导的雄激素丢失将导致骨微环境中IL-6表达增加。为了证明我们的假设，我们评估了睾丸切除对骨髓和脾脏中IL-6蛋白和mRNA表达的影响。我们发现睾丸切除术与术后3天和28天血清IL-6水平升高有关。佛波酯刺激的IL-6水平也更高的骨髓和脾细胞培养的睾丸切除小鼠与未手术或假手术的小鼠相比，上清液。此外，我们发现稳态IL-6 mRNA水平在骨髓中增加，而不是脾细胞。最后，我们发现睾丸切除的小鼠有脾肿大和骨髓细胞增多。脾脏组织学检查显示淋巴样增生伴红髓显著单核细胞浸润。我们的结论是睾丸切除术诱导IL-6在骨髓中的表达。这些结果表明，内分泌和细胞因子的相互作用有助于骨病理生理。
Interleukin-6 (IL-6) appears to be an important factor in disease states associated with bone resorption. There is bothin vitroandin vivoevidence supporting the fact that androgens down-regulate interleukin-6 production. These observations, in combination with the fact that osteoblasts and bone marrow stromal cells produce IL-6, led us to hypothesize that orchiectomy-induced androgen loss will result in increased IL-6 expression in the bone microenvironment. To prove our hypothesis we assessed the effect of orchiectomy on IL-6 protein and mRNA expression in bone marrow and spleen. We found that orchiectomy was associated with increased serum IL-6 levels at 3 and 28 days postsurgery. Phorbol ester-stimulated IL-6 levels were also higher in supernatants from bone marrow and spleen cell cultures from orchiectomized mice compared with unoperated or sham-operated mice. Additionally, we found that steady state IL-6 mRNA levels were increased in bone marrow but not spleen cells. Finally, we found that orchiectomized mice had splenomegaly and increased bone marrow cellularity. Histopathology of the spleen revealed lymphoid hyperplasia accompanied by a marked mononuclear cell infiltration of the red pulp. We conclude that orchiectomy induces IL-6 expression in the bone marrow. These findings suggest that endocrine and cytokine interactions contribute to bone pathophysiology.