介白素27被研究用於多发性硬化症

（德国杜塞尔多夫）－介白素27（IL-27），一个已知对T细胞有抗发炎反应的细胞激素，可能也会促进影响多发性硬化症的自然杀手细胞。这些是发表在第25届欧洲多发性硬化症治疗与研究（ECTRIMS）会议的初期研究结果。
　　
主要研究者，来自麻州波士顿哈佛神经疾病医学中心机构的Alice Laroni医师向Medscape神经学表示，IL-27对於自然杀手细胞群有抗增殖作用，将它们转变为比较活化的表现型。
　　
虽然多发性硬化症大部分被认为是T细胞调控的疾病，研究者们指出，研究显示自然杀手细胞可能也扮演部分角色。
　　
Laroni医师及其团队从健康捐赠者的血块层分离出自然杀手细胞，接著，他们将细胞分成CD56亮与CD56暗，且在不同的环境下，在有或是无IL-27的状况下培养这些细胞。
　　
然后评估表面标记的增殖、表现、转译因子与细胞激素分泌。透过细胞毒性检验，研究者们确认IL-27对自然杀手细胞的功能相关性。他们也比较从健康捐赠者、以及多发性硬化症病患分离出自然杀手细胞的IL-27受体表现。
　　
研究者们假提议，活体外CD56亮与CD56暗自然杀手细胞群都会表现IL-27受体。然而，他们观察到CD56亮细胞的IL-27受体表现增加。
　　
Laroni医师表示，在活化后，研究者们进一步放大IL-27受体。IL-27的增加降低了CD56亮与暗细胞的增殖，而CD56暗细胞群的效应比较强烈。但是，她指出，增殖作用降低、活化标记与细胞激素表现增加有关。
　　
麻州剑桥的Jacob Elkins医师在会后的一项访谈中表示，我想这是这些发现最有趣的一面。我们对於IL-27仍然有许多要学的。
　　
【细胞激素可能也会活化自然杀手细胞】
Laroni医师解释，基因分析与功能性研究显示，IL-27也会增加自然杀手细胞的细胞毒性潜力。她表示，我们发现接受免疫调节药物治疗的多发性硬化症病患，IL-27受体在自然杀手细胞亚群表面的表现不同。
　　
研究者们表示，免疫调节药物的部分治疗效果会与自然杀手细胞亚群对IL-27的反应增加有关。
　　
在她的演讲结束后，担任座长，来自丹麦根本哈根大学的Finn Sellebjerg医师问到，介白素10，也因为其抗发炎作用闻名，是否也扮演一个角色。
　　
Laroni医师回答，她并不这样想。穿透素（Perforin），一种存在於T细胞颗粒与自然杀手细胞的细胞溶解蛋白，可能牵涉其中，但是，这些只是初期研究结果。
　　
Laroni医师是预计在週六受奖的年轻研究者奖项得主。
　　
研究者们表示没有相关资金上的往来。

Interleukin 27 Investigated for Multiple Sclerosis

 
 
September 11, 2009 (Dusseldorf, Germany) — Interleukin 27 (IL-27), a cytokine known for its anti-inflammatory effect on T cells, might also prompt natural killer cells influencing multiple sclerosis. These are the findings of preliminary research presented here at the 25th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

"IL-27 has an antiproliferative effect on natural killer cell subsets, skewing them toward a more activated phenotype," lead investigator Alice Laroni, MD, from the Harvard Institute of Medicine Center for Neurologic Diseases in Boston, Massachusetts, told Medscape Neurology.

Although multiple sclerosis is largely considered a T-cell-mediated disease, the researchers point to studies suggesting that natural killer cells may also play a role.

Dr. Laroni and her team isolated natural killer cells from the buffy coat of healthy donors. They then sorted cells into CD56 bright and CD56 dim and cultured the cells under different conditions either with or without IL-27.

Proliferation, expression of surface markers, transcription factors, and cytokine secretion were then assessed. Using cytotoxicity assays, the researchers determined the functional relevance of IL-27 on natural killer cells. They also compared the expression of IL-27 receptor among natural killer cells isolated from healthy donors and patients with multiple sclerosis.

Investigators propose that the IL-27 receptor is expressed by both ex vivo isolated CD56 bright and CD56 dim natural killer cells subsets. However, they observed an increased expression on CD56 bright cells.

After activation, researchers further amplified the IL-27 receptor. "The addition of IL-27 decreased the proliferation of both CD56 bright and CD56 dim cells, with a stronger effect on the CD56 dim subset," Dr. Laroni said. But, she noted, decreased proliferation correlated with increased expression of activation markers and cytokines.

"I think this is the most interesting aspect of the findings," Jacob Elkins, MD, from Cambridge, Massachusetts, said during an interview after the session. "We still have a lot to learn about IL-27."

Cytokine May Also Activate Natural Killer Cells

Dr. Laroni explained that gene analysis and functional studies suggested that IL-27 also increased the cytotoxic potential of natural killer cells. "We found differential expression of IL-27 receptor on the surface of natural killer cell subsets in multiple sclerosis patients treated with immunomodulatory drugs," she noted.

Part of the therapeutic effect of immunomodulatory drugs could be related to increasing the responsiveness of natural killer cell subsets to IL-27, the researchers note.

During the question period after her talk, session cochair Finn Sellebjerg, MD, from the University of Copenhagen in Denmark, asked whether interleukin 10, also known for its anti-inflammatory effect, may be playing a role.

Dr. Laroni answered that she does not think so. Perforin, a cytolyic protein in the granules of T cells and natural killer cells, might be involved, she suggested, "but these are preliminary results."

Dr. Laroni is among the young researchers being considered for an award scheduled to be presented Saturday.

The researchers have disclosed no relevant financial relationships.

European Committee for Treatment and Research in Multiple Sclerosis: Abstract 9. Presented September 9, 2009.