Barton Nicola J, Stevens David A, Hughes Jane P, Rossi Adriano G, Chessell Iain P, Reeve Alison J, McQueen Daniel S
Division of Neuroscience, University of Edinburgh, Medical College, 1 George Sq, Edinburgh, EH8 9JZ, UK.
J Inflamm (Lond). 2007 Jun 13;4:13. doi: 10.1186/1476-9255-4-13.
The inflammation that accompanies the pain and swelling associated with osteo- and rheumatoid arthritis is mediated by complex interactions of inflammatory mediators. Cytokines play a pivotal role in orchestrating many of these processes, including inflammatory cell recruitment, adhesion and activation. In addition, prostaglandins are secreted into the synovial cavity and are involved in perpetuation of local inflammation, vasodilatation and vasoconstriction, and also with bone resorption. Pre-clinical models have been developed in order to correlate to the human disease and principle among these is the adjuvant-induced arthritis model in the rat.
We have developed a technique to quantitatively assess the contents of synovial fluid samples from rat joints. Two needles joined together are inserted into the knee joint of anaesthetised rats and connected to a Watson-Marlow perfusion pump. Sterile saline is infused and withdrawn at 100 microl min-1 until a 250 microl sample is collected.
Our results demonstrate up to 125 fold increases in synovial IL1alpha and IL1beta concentrations, approximately 30 fold increases in levels of IL6 and IL10 and a 200-300 fold elevation in synovial concentrations of TNFalpha during FCA-induced experimental arthritis. Finally, this novel technique has demonstrated a dose-response relationship between FCA and the total cell counts of synovial perfusates.
In summary, this new technique provides a robust method for quantifying inflammatory mediators and cells from the synovial cavity itself, thereby detailing the inflammatory processes from within the capsule and excluding those processes occurring in other tissues surrounding the entire articulation.
骨关节炎和类风湿性关节炎所伴有的疼痛和肿胀相关的炎症是由炎症介质的复杂相互作用介导的。细胞因子在协调许多这些过程中起关键作用,包括炎症细胞的募集、黏附和激活。此外,前列腺素分泌到滑膜腔中,参与局部炎症的持续、血管舒张和收缩,还与骨吸收有关。为了与人类疾病相关联,已经开发了临床前模型,其中主要的是大鼠佐剂诱导性关节炎模型。
我们开发了一种技术来定量评估大鼠关节滑液样本的成分。将两根连接在一起的针插入麻醉大鼠的膝关节,并连接到沃森-马洛灌注泵。以100微升/分钟的速度注入和抽取无菌生理盐水,直到收集到250微升样本。
我们的结果表明,在弗氏完全佐剂(FCA)诱导的实验性关节炎期间,滑膜白细胞介素1α(IL1α)和白细胞介素1β(IL1β)浓度增加高达125倍,白细胞介素6(IL6)和白细胞介素10(IL10)水平增加约30倍,滑膜肿瘤坏死因子α(TNFα)浓度升高200 - 300倍。最后,这项新技术证明了FCA与滑膜灌洗液总细胞计数之间的剂量反应关系。
总之,这项新技术提供了一种强大的方法来定量滑膜腔内的炎症介质和细胞,从而详细描述关节囊内的炎症过程,并排除整个关节周围其他组织中发生的那些过程。