Ottaviani Robert A, Wooley Paul, Song Zheng, Markel David C
Department of Orthopaedic Surgery, Wayne State University School of Medicine, Detroit, MI 48201, USA.
J Bone Joint Surg Am. 2007 Jan;89(1):148-57. doi: 10.2106/JBJS.E.01135.
Intra-articular injection of hyaluronan preparations is a popular treatment for osteoarthritis of the knee. Recently, clinical reports have described acute inflammatory reactions in joints following these injections. The purpose of this study was to use a murine pouch model to study the local inflammatory and possibly immunological effects of three commercially available hyaluronan-derived products.
Each of three different hyaluronan products (Synvisc, Hyalgan, and Supartz) was injected into air pouches established in groups of BALB/c mice. A positive control group (with particle-induced inflammation) and a negative control group (injected with saline solution) were also included. After fourteen days, the mice were killed and the air pouches were explanted and prepared for histological evaluation of the local inflammatory reaction. The antibody response was measured with use of ELISA (enzyme-linked immunosorbent assay) of serum samples obtained after the mice were killed.
Histological analysis revealed a significant increase in total membrane cellularity (p < 0.001 to p < 0.03) after the use of all hyaluronan preparations. The increased cellularity was attributed to an inflammatory cell influx, rather than accumulation of fibroblasts, and elevated lymphocyte counts were observed in membranes stimulated by Synvisc (hylan G-F 20). The ELISA data revealed an antibody response to the Synvisc preparation. This immunological response was directed against a non-hyaluronan portion of the product, as indicated by the lack of cross-reactivity with the other hyaluronan products.
These findings demonstrate that all three hyaluronan preparations, as currently manufactured, can cause an inflammatory soft-tissue reaction, but only the non-hyaluronan portion of the Synvisc product created an immunological response. It appears likely that this component may be the target of adverse responses in patients.
关节腔内注射透明质酸制剂是治疗膝关节骨关节炎的常用方法。最近，临床报告描述了这些注射后关节内的急性炎症反应。本研究的目的是使用小鼠气囊模型来研究三种市售透明质酸衍生产品的局部炎症及可能的免疫作用。
将三种不同的透明质酸产品（施沛特、海乐妙和苏帕同）分别注射到BALB/c小鼠组建立的气囊肿内。还包括一个阳性对照组（颗粒诱导炎症）和一个阴性对照组（注射盐溶液）。14天后，处死小鼠，取出气囊肿并进行组织学评估以观察局部炎症反应。使用酶联免疫吸附测定法（ELISA）检测处死小鼠后获得的血清样本的抗体反应。
组织学分析显示，使用所有透明质酸制剂后，总膜细胞数显著增加（p<0.001至p<0.03）。细胞数增加归因于炎症细胞流入，而非成纤维细胞积累，并且在施沛特（交联透明质酸钠凝胶G-F 20）刺激的膜中观察到淋巴细胞计数升高。ELISA数据显示对施沛特制剂有抗体反应。如与其他透明质酸产品缺乏交叉反应所示，这种免疫反应针对的是该产品的非透明质酸部分。
这些发现表明，目前生产的所有三种透明质酸制剂均可引起炎症性软组织反应，但只有施沛特产品的非透明质酸部分产生了免疫反应。看来该成分可能是患者不良反应的靶点。
