Freysdottir Jona, Hardardottir Ingibjorg, Gizurarson Sveinbjorn, Vikingsson Arnor
Lyfjathroun hf-Biopharmaceuticals, Reykjavik, Iceland.
J Clin Immunol. 2007 May;27(3):284-93. doi: 10.1007/s10875-007-9081-3. Epub 2007 Mar 14.
Mucosal tolerance has been shown to reduce disease severity in animal models mimicking human autoimmune diseases. The objective of this study was to examine whether mucosal tolerance against keyhole limpet haemocyanin (KLH) could be used to reduce bovine serum albumin (BSA)-induced arthritis in rats and whether anti-inflammatory drugs or passive cigarette smoke affected tolerance induction. Arthritis was induced by immunizing rats with BSA and then injecting BSA into one knee and saline into the other knee for comparison. Prior to BSA immunization, the rats were treated intranasally with KLH or saline and KLH then injected in the knee joints at the time of BSA injection, or the rats were treated with or without anti-inflammatory drugs or subjected to cigarette smoke prior to and during intranasal treatment with BSA. The rats that received intranasal treatment with KLH had a significantly less inflammation in their left knee joint compared to rats that received intranasal saline treatment. Beclamethasone increased the tolerance effect of BSA, whereas passive cigarette smoke abrogated the mucosal tolerance. This data suggests that bystander suppression can be used to treat arthritis and other autoimmune diseases, even when the autoantigen is not known.
在模拟人类自身免疫性疾病的动物模型中，黏膜耐受已被证明可降低疾病严重程度。本研究的目的是检验针对钥孔戚血蓝蛋白（KLH）的黏膜耐受是否可用于减轻大鼠牛血清白蛋白（BSA）诱导的关节炎，以及抗炎药物或被动吸烟是否会影响耐受诱导。通过用BSA免疫大鼠，然后向一侧膝关节注射BSA，另一侧膝关节注射生理盐水进行比较来诱导关节炎。在BSA免疫前，大鼠经鼻内给予KLH或生理盐水，然后在注射BSA时将KLH注射到膝关节中，或者在鼻内给予BSA治疗之前和期间，大鼠接受或不接受抗炎药物治疗或暴露于香烟烟雾中。与接受鼻内生理盐水治疗的大鼠相比，接受鼻内KLH治疗的大鼠左膝关节炎症明显减轻。倍氯米松增强了BSA的耐受效果，而被动吸烟则消除了黏膜耐受。该数据表明，即使自身抗原未知，旁观者抑制也可用于治疗关节炎和其他自身免疫性疾病。
