JLB：为何有些流感患者病情重

cao1976

原贴由david04224发表于 2009-5-26 22:25
http://biosky.haotui.com/thread-9830-1-9.html

甲型H1N1流感正在一些国家肆虐，但一些患者的病情明显比其他患者严重。美国研究人员推测，其原因之一可能是流感病毒会使某些患者的免疫系统在较长时间内功能失常，从而容易感染其他细菌，使这些人患上肺炎等更严重的疾病。

这项研究由费城儿童医院过敏和免疫学部主任凯瑟琳·沙利文领导完成，研究成果5月4日发表在《白细胞生物学杂志》网络版上。

研究人员调查了一些患有重度流感的儿科患者血浆中的细胞因子水平。细胞因子是一类能在细胞间传递信息、具有免疫调节功能的蛋白质或小分子多肽。

结果发现，虽然上述患者血浆中的细胞因子水平有所升高，但他们体内toll样受体的反应却有所减少。toll样受体是先天性免疫系统的重要受体，可识别不同病原体，并在细菌入侵时激活快速先天免疫反应。此外，它还可以调节获得性免疫，是连接先天性免疫与获得性免疫的桥梁。

研究人员推测，toll样受体活性降低导致部分流感患者免疫系统功能失常，这增加了二次感染的机会。沙利文表示，这项研究有助于解释为何一些流感患者仅仅是感冒而已，另一些患者却病情严重甚至因此丧命；也可以解释为何在因为流感而死亡的儿童中，四分之一的人其实死于细菌感染。

《白细胞生物学杂志》副主编约翰·惠里评价说，尽管近几十年来人类在医学上取得了巨大进展，但流感病毒一直是个巨大威胁。这项新研究使人们更进一步了解流感，将有助于采取有效的治疗措施。（生物谷Bioon.com）

生物谷推荐原始出处：

Journal of Leukocyte Biology, doi:10.1189/jlb.1108710

Immune dysregulation in severe influenza

Meredith L. Heltzer *, Susan E. Coffin , Kelly Maurer *, Asen Bagashev *, Zhe Zhang , Jordan S. Orange *, and Kathleen E. Sullivan *

Divisions of *Allergy and Immunology and Infectious Diseases and Center for Biomedical Informatics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

Among previously healthy children with severe influenza, the mechanisms leading to increased pathology are not understood. We hypothesized that children with severe influenza would have high levels of circulating cytokines. To examine this, we recruited patients with severe influenza and examined plasma cytokine levels as well as the ability of peripheral blood cells to respond to stimuli. Ten patients with severe influenza were enrolled during the 2005–2007 influenza seasons. We evaluated plasma cytokine levels, circulating NK cells, and responses to TLR ligands during the illness. We compared these patients with five patients with moderate influenza, six patients with respiratory syncytial virus (RSV), and 24 noninfected controls. Patients with influenza showed depressed responses to TLR ligands when compared with RSV patients and healthy controls (P<0.05). These normalized when retested during a convalescent phase. Plasma levels of IL-6, IL-12, and IFN- were elevated in influenza patients compared with controls (P<0.05). A compromised ability to produce TNF- was reproduced by in vitro infection, and the magnitude of the effect correlated with the multiplicity of infection and induction of IFN regulatory factor 4 expression. Aberrant, systemic, innate responses to TLR ligands during influenza infection may be a consequence of specific viral attributes such as a high inoculum or rapid replication and may underlie the known susceptibility of influenza-infected patients to secondary bacterial infections.