Soilu-Hänninen M, Röyttä M, Salmi A, Salonen R
Department of Virology, University of Turku, Finland.
J Neuroimmunol. 1997 Jan;72(1):95-105. doi: 10.1016/s0165-5728(96)00158-0.
Experimental allergic encephalomyelitis (EAE) is facilitated in resistant BALB/c mice by intraperitoneal infection with an avirulent Semliki Forest virus (SFV-A7). Viral infection increases the incidence of EAE from 15-30% to 60-90% and speeds up appearance of paralysis from 24 to 14 days. In this paper, we describe treatment of virus-facilitated EAE with monoclonal antibodies (mAbs) against leukocyte and/or endothelial cell adhesion molecules. Therapy with mAb against ICAM-1 (intercellular adhesion molecule-1) had a modest effect, but caused hemorrhagic brain and spinal cord lesions. Therapy with mAb against Mac-1 (alpha M beta 2-integrin) was well tolerated but had no effect. Therapy with mAb against VLA-4 (alpha 4 beta 1-integrin) was safe, diminished both clinical and histopathological signs of EAE, decreased induction of VCAM-1 (vascular cell adhesion molecule-1) on brain vessels and diminished infiltration of VLA-4+ cells into the brain. The amount of viral antigen in the brain was not altered. We conclude that facilitation of leukocyte entry into the brain is a major mechanism for viral facilitation of EAE in the BALB/c mouse, and that facilitation can be inhibited by anti-adhesion therapy. This may have implications for treatment of relapses triggered by viral infections in multiple sclerosis.
实验性变应性脑脊髓炎（EAE）在具有抗性的BALB/c小鼠中可通过腹腔感染无毒力的Semliki森林病毒（SFV-A7）而被促进。病毒感染使EAE的发病率从15% - 30%增加到60% - 90%，并使麻痹出现的时间从24天加快到14天。在本文中，我们描述了用针对白细胞和/或内皮细胞黏附分子的单克隆抗体（mAb）治疗病毒促进型EAE的情况。用抗ICAM-1（细胞间黏附分子-1）的mAb进行治疗有一定效果，但会导致脑和脊髓出血性病变。用抗Mac-1（αMβ2整合素）的mAb进行治疗耐受性良好但无效。用抗VLA-4（α4β1整合素）的mAb进行治疗是安全的，可减轻EAE的临床和组织病理学症状，减少脑血管上VCAM-1（血管细胞黏附分子-1）的诱导，并减少VLA-4+细胞向脑内的浸润。脑中病毒抗原的量未改变。我们得出结论，促进白细胞进入脑内是BALB/c小鼠中病毒促进EAE的主要机制，并且这种促进作用可通过抗黏附治疗来抑制。这可能对治疗多发性硬化症中由病毒感染引发的复发有影响。
