Ichiyama Takashi, Kajimoto Madoka, Suenaga Naoko, Maeba Shinji, Matsubara Tomoyo, Furukawa Susumu
Yamaguchi University School of Medicine, Japan.
J Neuroimmunol. 2006 Mar;172(1-2):182-6. doi: 10.1016/j.jneuroim.2005.10.010.
In multiple sclerosis, there have been many reports on matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). However, MMPs and TIMPs have not been reported in acute disseminated encephalomyelitis (ADEM). We determined the relationship between the serum concentrations of MMP-9 and TIMP-1 and activity of lesions on MRI in 14 patients with ADEM to investigate the roles of MMP-9 and TIMP-1 in the pathogenesis of ADEM. Serum MMP-9 and TIMP-1 levels, measured by ELISA and gadolinium-enhanced (Gd+) brain MRI, were analyzed. Serum MMP-9 and TIMP-1 levels at the acute stage were higher than controls, and the serum MMP-9 levels at the acute stage were higher than those at the convalescent stage in ADEM. In seven patients with Gd+ lesions on brain MRI, serum MMP-9 levels and the MMP-9/TIMP-1 ratio at the acute stage were higher than those at the convalescent stage, and serum TIMP1 levels at the acute stage were lower than those at the convalescent stage. In seven patients without Gd+ lesions on brain MRI, serum TIMP-1 levels at the acute stage were higher than those at the convalescent stage. We speculated that MMP-9 is related to lesion formation at the early stage in ADEM and that TIMP-1 is induced to modulate MMP-9 activity. These findings suggest that MMP-9 and TIMP-1 secondarily play some roles in the inflammatory cascade of ADEM.
在多发性硬化症中,已有许多关于基质金属蛋白酶(MMPs)及其组织抑制剂(TIMPs)的报道。然而,急性播散性脑脊髓炎(ADEM)中尚未见有关MMPs和TIMPs的报道。我们测定了14例ADEM患者血清中MMP-9和TIMP-1的浓度与MRI上病灶活性之间的关系,以研究MMP-9和TIMP-1在ADEM发病机制中的作用。分析了通过酶联免疫吸附测定法(ELISA)测得的血清MMP-9和TIMP-1水平以及钆增强(Gd+)脑MRI结果。ADEM急性期血清MMP-9和TIMP-1水平高于对照组,且急性期血清MMP-9水平高于恢复期。在7例脑MRI有Gd+病灶的患者中,急性期血清MMP-9水平及MMP-9/TIMP-1比值高于恢复期,急性期血清TIMP-1水平低于恢复期。在7例脑MRI无Gd+病灶的患者中,急性期血清TIMP-1水平高于恢复期。我们推测MMP-9与ADEM早期病灶形成有关,而TIMP-1被诱导来调节MMP-9的活性。这些发现提示MMP-9和TIMP-1在ADEM的炎症级联反应中起一些次要作用。