Interferon response heterogeneity:: activation of a pro-inflammatory response by interferonα and β.: A possible basis for diverse responses to interferonβ in MS
Interferon response heterogeneity:: activation of a pro-inflammatory response by interferonα and β.: A possible basis for diverse responses to interferonβ in MS
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DOI：
10.1002/jlb.65.4.439
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发表时间：
1999-04-01
影响因子：
5.5
通讯作者：
Reinhard, JF
中科院分区：
文献类型：
--
作者：
Jansen, M;Reinhard, JF
干扰素-γ刺激(致炎)型干扰素受体，可加重多发性硬化症(MS)，而干扰素-α和β-干扰素是(抗炎)I型干扰素受体的配体，对某些(但不是全部)MS患者有益。如果干扰素-β引起II型促炎反应，其有益作用可能会减弱。这些研究是通过使用喹啉酸(Quin)的形成作为II型受体激活的测量来测试这种可能性的。在正常的人巨噬细胞培养中，干扰素-γ对Quin的形成是最有效的刺激。一般来说，干扰素-β和干扰素-α的效力较弱。然而，观察到了意想不到的患者间差异。在一些受试者中，干扰素-α比干扰素-β更有效，在另一些受试者中，干扰素-β比干扰素-α更有效。目前的数据表明，在接触干扰素后，Quin生产的受试者之间存在差异。对干扰素-β表现出促炎反应的多发性硬化症患者(例如，增加的奎宁)可能不太可能从这种治疗中受益。
Interferon gamma (TFN-gamma) stimulates the (proinflammatory) type IT interferon receptor and is known to exacerbate multiple sclerosis (MS), In contrast, IFN-alpha and IFN-beta are ligands for the (anti-inflammatory) type I interferon receptor and are beneficial in some (but not all) patients with MS. Should IFN-beta elicit a type-II-like pro-inflammatory response, the beneficial effects might be attenuated. These studies were undertaken to test this possibility with the use of quinolinic acid (QUIN) formation as a measure of type II receptor activation. In normal human macrophage cultures, IFN-gamma was the most potent stimulus for QUIN formation. Generally, IFN-beta and IFN-alpha were less potent. However, an unexpected inter-patient variability was observed. In some subjects, IFN-alpha was more potent than IFN-beta, In other subjects, IFN-beta was more potent than IFN-alpha. The present data demonstrate an inter-subject variability for QUIN production following exposure to the interferons. MS patients who demonstrate a pro-inflammatory response to IFN-beta (e.g., increased QUIN) may be less likely to benefit from this therapy.