Treon S P, Anderson K C
Dana Farber Cancer Institute, Boston, MA 02115, USA.
Curr Opin Hematol. 1998 Jan;5(1):42-8.
Since the discovery a decade ago that interleukin-6 is a growth factor for human multiple myeloma (MM) cells, great strides have been made in understanding the relationship of this cytokine to multiple myeloma. A plethora of studies on this topic has confirmed that interleukin-6 is a key growth and survival factor for myeloma cells, as well as a major morbidity factor for patients with MM. Their is strong evidence for both an autocrine (in MM cells) as well as a paracrine sources of interleukin-6 induction (from bone marrow stromal cells and osteoblast cells), with bone marrow stromal cells likely serving as the main center of production of interleukin-6 in patients with MM. Moreover, bone marrow stromal cells from patients with MM express viral interleukin-6, a functional homolog of human interleukin-6 that is produced by Kaposi's sarcoma-associated herpesvirus and may further enhance MM cell growth and survival. Soluble interleukin-6 receptor serum levels are elevated in patients with MM; soluble interleukin-6 receptor may amplify circulating interleukin-6 in patients with MM, and complex with interleukin-6, resulting in proliferation of MM cells that either express low or no detectable surface interleukin-6 receptor. Recent advances in our understanding of interleukin-6 signaling cascades mediating MM growth and survival, as well as its impact on cell cycle regulation in MM cells, may lead to therapeutics designed to interfere with these pathways. Finally, considerable progress has been made in identifying and developing agents including antibodies, biologic agents, hormones and drugs that interfere with the interleukin-6 signaling pathways and may therefore have a role in the treatment of MM.
自十年前发现白细胞介素-6是人类多发性骨髓瘤（MM）细胞的生长因子以来，在理解这种细胞因子与多发性骨髓瘤的关系方面已经取得了巨大进展。关于这一主题的大量研究证实，白细胞介素-6是骨髓瘤细胞的关键生长和存活因子，也是MM患者的主要发病因素。有强有力的证据表明白细胞介素-6的诱导存在自分泌（在MM细胞中）以及旁分泌来源（来自骨髓基质细胞和成骨细胞），骨髓基质细胞可能是MM患者中白细胞介素-6的主要产生中心。此外，MM患者的骨髓基质细胞表达病毒白细胞介素-6，它是人类白细胞介素-6的功能同源物，由卡波西肉瘤相关疱疹病毒产生，可能进一步促进MM细胞的生长和存活。MM患者的可溶性白细胞介素-6受体血清水平升高；可溶性白细胞介素-6受体可能会放大MM患者循环中的白细胞介素-6，并与白细胞介素-6形成复合物，导致表达低水平或无法检测到表面白细胞介素-6受体的MM细胞增殖。我们对介导MM生长和存活的白细胞介素-6信号级联反应及其对MM细胞周期调控的影响的最新认识进展，可能会带来旨在干扰这些途径的治疗方法。最后，在识别和开发包括抗体、生物制剂、激素和药物在内的能够干扰白细胞介素-6信号通路并因此可能在MM治疗中发挥作用的药物方面已经取得了相当大的进展。
