Kleinau S, Larsson P, Björk J, Holmdahl R, Klareskog L
Department of Medical and Physiological Chemistry, Uppsala University, Sweden.
Clin Exp Immunol. 1989 Oct;78(1):138-42.
The effects of the immunomodulatory drug Linomide (LS-2616) have been investigated on two variants of collagen-induced arthritis (CIA) in Lewis rats, i.e. arthritis induced either with heterologous (bovine) or with homologous (rat) collagen type II (CII). Treatment with Linomide from the day of immunization (prophylactic) had a mild ameliorative effect on the severity of arthritis in the heterologous CIA, while the homologous CIA was strongly augmented. In both models, Linomide treatment caused a more severe arthritis when given from onset of clinical signs of disease and onwards (therapeutic). Serum antibody levels to CII were significantly decreased by prophylactic Linomide treatment in rats immunized with heterologous CII, while elevated levels of anti-rat CII antibodies were seen in the homologous model. No effect on antibody levels was seen with the therapeutic treatment regime. The opposing effects of prophylactic treatment with Linomide in heterologous versus homologous CIA indicate that the immune response to an autoantigen may be regulated differently from that to a foreign antigen. These results further strengthen the view that heterologous and homologous CIA should be regarded as separate experimental models, and that the studies on homologous CIA may represent a novel approach for future studies of autoimmune responses and evaluation of anti-rheumatic drugs.
免疫调节药物利诺米德（LS - 2616）对Lewis大鼠胶原诱导性关节炎（CIA）的两种变体的作用已得到研究，这两种变体分别是由异源（牛）或同源（大鼠）II型胶原（CII）诱导的关节炎。从免疫当天开始用利诺米德治疗（预防性治疗）对异源CIA的关节炎严重程度有轻微改善作用，而同源CIA则明显加重。在这两种模型中，从疾病临床症状出现开始及之后给予利诺米德治疗（治疗性治疗）会导致更严重的关节炎。在用异源CII免疫的大鼠中，预防性利诺米德治疗可使血清中针对CII的抗体水平显著降低，而在同源模型中则观察到抗大鼠CII抗体水平升高。治疗性治疗方案对抗体水平没有影响。利诺米德在异源与同源CIA中的预防性治疗的相反作用表明，对自身抗原的免疫反应可能与对外源抗原的免疫反应调控方式不同。这些结果进一步强化了以下观点，即异源和同源CIA应被视为不同的实验模型，并且对同源CIA的研究可能代表了未来自身免疫反应研究和抗风湿药物评估的一种新方法。
