一項(xiàng)最新研究證實(shí)IL9調(diào)節(jié)肥大細(xì)胞，這種細(xì)胞釋放介質(zhì)導(dǎo)致氣管或者支氣管氣道收縮。這種氣道超敏（AHR）損害氣流進(jìn)入肺部，這項(xiàng)研究結(jié)果可以用于研制開發(fā)哮喘治療的新藥物。

2005年5月在美國圣地亞哥舉行的美國胸科學(xué)會年會上，來自MedImmune的研究人員報(bào)道了這些研究結(jié)果。他們的數(shù)據(jù)證實(shí)：IL9對AHR的作用，依賴于肥大細(xì)胞的增殖和成熟。在該項(xiàng)研究中，肥大細(xì)胞的過度表達(dá)與肺部兩種高水平的介質(zhì)有關(guān)：半胱氨酰白三烯(CystLTs)和前列腺素E2 (PGE2)，已經(jīng)知道這些介質(zhì)能夠直接作用于平滑肌細(xì)胞，與內(nèi)源性氣道張力的改變有關(guān)，表現(xiàn)為AHR。

IL9與哮喘癥狀有關(guān)，包括黏液分泌、肺部炎癥細(xì)胞浸潤、以及IgE的生成。MedImmune正在評估IL9單克隆抗體治療或者預(yù)防癥狀性、中度~重度、持續(xù)性哮喘。該公司已經(jīng)在健康受試者完成了該公司的抗IL9單克隆抗體的I期劑量梯度探索、靜脈注射臨床試驗(yàn)。下一步，該公司計(jì)劃開始皮下注射給藥的II期臨床劑量探索試驗(yàn)。

MedImmune公司的研究部高級主任Anthony Coyle博士說：“我們期望研制開發(fā)出阻斷IL9的抗體治療方法，這可能減少肥大細(xì)胞來源的與哮喘以及其他疾病相關(guān)的因子。”

MAbs to Target IL-9 in Asthma
 
A new study has demonstrated that interleukin-9 (IL-9) regulates mast cells, which release mediators that cause the bronchi or bronchial airway to constrict. This airway hyperreactivity (AHR) impairs airflow into the lungs, a finding being used to develop a new therapy for asthma.

The findings were presented at the annual meeting of the American Thoracic Society in San Diego (CA, USA) in May 2005 by researchers from MedImmune, Inc. (Gaithersburg, MD, USA). Their data demonstrated that IL-9’s effect on AHR depended on the proliferation and maturation of mast cells. In the study, overexpression of mast cells was associated with high lung levels of two mediators: cysteinyl leukotrienes (CystLTs) and prostaglandin E2 (PGE2), which are known to have direct effects on smooth muscle and have been previously associated with changes in intrinsic airway tone, manifesting as AHR.

IL-9 has been associated with symptoms of asthma, including mucous production, lung infiltration of inflammatory cells, and IgE production. MedImmune is evaluating the potential of monoclonal antibodies (MAbs) targeting IL-9 to treat or prevent symptomatic, moderate-to-severe, persistent asthma. The company has already completed a phase I dose-escalation, intravenously administered study in healthy adults with its lead anti-IL-9 MAb. Next, it plans to initiate a subcutaneously administered phase II dose-escalation study.

“We look forward to advancing the development of antibody therapies to block IL-9, which may have the potential to reduce mast cell-derived respiratory factors associated with asthma and other illnesses,” observed Anthony Coyle, Ph.D., senior director, research, at MedImmune.