Galle Pia, Jensen Lene, Andersson Christina, Cuzzocrea Salvatore, Di Paola Rosanna, Nicoletti Ferdinando, Svenson Morten, Bendtzen Klaus, Thomsen Allan R, Hansen Morten B
Department of Clinical Immunology, Rigshospitalet, National University Hospital, Copenhagen, Denmark.
Int Immunopharmacol. 2007 Dec 15;7(13):1704-13. doi: 10.1016/j.intimp.2007.08.026. Epub 2007 Sep 21.
IL-6 is involved in inflammation and a therapeutic target. 0.1% of Danish blood donors have nanomolar plasma concentrations of polyclonal, picomolar affinity and in vitro as well as in vivo neutralizing IgG autoantibodies to IL-6 (aAb-IL-6). Such donors are assumed to be severely IL-6 deficient; yet they appear healthy and do not exhibit overt clinical or laboratory abnormalities. We induced comparable levels of aAb-IL-6 in different mouse strains by vaccination with immunogenic IL-6 analogues. We observed that the induced aAb-IL-6 protected against collagen-induced arthritis and experimental allergic encephalitis. Furthermore, aAb-IL-6 carrying mice displayed increased plasma TNFalpha concentrations upon challenge with LPS. Taken together, induction of IL-6 autoantibodies was possible in different mouse strains. The autoantibodies influenced experimental inflammation. This immunotherapeutic principle might be a viable alternative in immune competent humans suffering from disorders driven by IL-6.
白细胞介素-6（IL-6）参与炎症反应且是一个治疗靶点。0.1%的丹麦献血者血浆中存在纳摩尔浓度的多克隆、皮摩尔亲和力且在体外及体内均能中和IL-6的IgG自身抗体（aAb-IL-6）。这些献血者被认为严重缺乏IL-6；然而他们看起来健康，且未表现出明显的临床或实验室异常。我们通过用免疫原性IL-6类似物进行疫苗接种，在不同小鼠品系中诱导出了相当水平的aAb-IL-6。我们观察到，诱导产生的aAb-IL-6可预防胶原诱导的关节炎和实验性变应性脑脊髓炎。此外，用脂多糖（LPS）攻击时，携带aAb-IL-6的小鼠血浆肿瘤坏死因子α（TNFα）浓度升高。综上所述，在不同小鼠品系中诱导产生IL-6自身抗体是可能的。这些自身抗体影响实验性炎症。对于患有由IL-6驱动的疾病的免疫功能正常的人类而言，这种免疫治疗原则可能是一种可行的替代方法。
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