López-Collazo Eduardo, Fuentes-Prior Pablo, Arnalich Francisco, del Fresno Carlos
Research Unit, La Paz Hospital, Madrid, Spain.
Curr Opin Infect Dis. 2006 Jun;19(3):237-44. doi: 10.1097/01.qco.0000224817.35105.7d.
The pseudo-kinase interleukin-1 receptor-associated kinase-M has emerged as a critical molecule in the down-regulation of inflammatory responses. Dysregulation of the toll-like receptor-interleukin-1 receptor-associated kinase system, and in particular interleukin-1 receptor-associated kinase-M up-regulation, are associated with a number of pathologies. This review highlights recent findings on interleukin-1 receptor-associated kinase-M reported in biomedical literature.
Interleukin-1 receptor-associated kinase-M plays a critical role in generating a refractory state of the immune system following monocytes/macrophages encounter with bacteria or tumor cells. This state has been demonstrated so far in patients who suffer from sepsis, leukemia, and acute coronary syndrome, and seems to be associated with interleukin-1 receptor-associated kinase-M overexpression in their circulating monocytes. In addition, the pseudo-kinase represents a central regulator of osteoclast differentiation and activation, and might thus be related to the onset of osteoporosis.
Interleukin-1 receptor-associated kinase-M is involved in the control of endotoxin tolerance in monocytes, in osteoporosis, as well as in the deactivation of tumor-infiltrating macrophages. Additionally, patients who suffer from several pathologies related to inflammatory responses express high levels of this molecule in their circulating monocytes. Human monocytes treated with a nitric oxide donor also express large amounts of interleukin-1 receptor-associated kinase-M, apparently under the control of tumor necrosis factor-alpha. This mechanism could explain the induction of interleukin-1 receptor-associated kinase-M in monocytes from patients who suffer from an inflammatory pathology.
假激酶白细胞介素-1受体相关激酶M已成为炎症反应下调中的关键分子。Toll样受体-白细胞介素-1受体相关激酶系统失调，特别是白细胞介素-1受体相关激酶M上调，与多种病理状况相关。本综述重点介绍生物医学文献中报道的关于白细胞介素-1受体相关激酶M的最新发现。
白细胞介素-1受体相关激酶M在单核细胞/巨噬细胞与细菌或肿瘤细胞接触后产生免疫系统不应答状态中起关键作用。迄今为止，在患有败血症、白血病和急性冠状动脉综合征的患者中已证实了这种状态，并且似乎与他们循环单核细胞中白细胞介素-1受体相关激酶M的过表达有关。此外，该假激酶是破骨细胞分化和激活的核心调节因子，因此可能与骨质疏松症的发病有关。
白细胞介素-1受体相关激酶M参与单核细胞内毒素耐受性的控制、骨质疏松症以及肿瘤浸润巨噬细胞的失活。此外，患有几种与炎症反应相关病理状况的患者，其循环单核细胞中该分子表达水平较高。用一氧化氮供体处理的人单核细胞也大量表达白细胞介素-1受体相关激酶M，显然是在肿瘤坏死因子-α的控制下。这一机制可以解释炎症性疾病患者单核细胞中白细胞介素-1受体相关激酶M的诱导情况。
