van de Langerijt A G, van Lent P L, Hermus A R, van de Putte L B, van den Berg W B
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
Clin Exp Immunol. 1993 Oct;94(1):150-5. doi: 10.1111/j.1365-2249.1993.tb05993.x.
Inbred female Lewis (LEW/N) rats develop a severe chronic arthritis in the adjuvant arthritis (AA) model, histocompatible Fisher (F344/N) rats are resistant and germ-free Fishers (GF F344) are again susceptible. In this study we show that the F344 rat can become susceptible to AA, using Mycobacterium tuberculosis (M.tb.) in the powerful adjuvant paraffin oil, instead of mineral oil (Freund's incomplete adjuvant (FIA)). This indicates that the F344 rat does not lack T effector cells. To examine further mechanisms responsible for suppression, we determined the level of plasma corticosterone in response to IL-1 alpha in Lewis, F344 and GF F344 rats. IL-1 alpha induced only low amounts of corticosterone in Lewis rats, but high amounts in both F344 and GF F344 rats. The GF F344 rats are susceptible to AA, but the severity of the disease is reduced compared with Lewis rats. This indicates that corticosterone may be an important mechanism to suppress disease development, but not the only mechanism. In addition we investigated whether T suppressor cells play a role in the resistance of the F344 strain. This was performed by pretreating the animals with the immunomodulating drugs cyclophosphamide (Cy) and cyclosporin A (CsA). We were unable to make the F344 rat susceptible to AA, indicating that active suppression does not play a role in the induction phase of arthritis. This finding is confirmed in adoptive transfer experiments of AA from Lewis to F344 rats. Our data suggest the lack of a strong pre-existing suppression in the F344 rats, and indicate that suppression is generated upon bacterial challenge. Whether suppression is overruled probably depends on the power of adjuvants used and potential control by corticosteroids.
近交系雌性刘易斯（LEW/N）大鼠在佐剂性关节炎（AA）模型中会发展出严重的慢性关节炎，组织相容性的费希尔（F344/N）大鼠具有抗性，而无菌费希尔大鼠（GF F344）再次变得易感。在本研究中，我们表明，使用强大的佐剂石蜡油而非矿物油（弗氏不完全佐剂（FIA））中的结核分枝杆菌（M.tb.），F344大鼠可变得对AA易感。这表明F344大鼠并不缺乏T效应细胞。为了进一步研究负责抑制的机制，我们测定了刘易斯、F344和GF F344大鼠中白细胞介素-1α（IL-1α）刺激下的血浆皮质酮水平。IL-1α在刘易斯大鼠中仅诱导少量皮质酮，但在F344和GF F344大鼠中均诱导大量皮质酮。GF F344大鼠对AA易感，但与刘易斯大鼠相比，疾病严重程度有所降低。这表明皮质酮可能是抑制疾病发展的重要机制，但不是唯一机制。此外，我们研究了T抑制细胞是否在F344品系的抗性中发挥作用。这是通过用免疫调节药物环磷酰胺（Cy）和环孢素A（CsA）预处理动物来进行的。我们无法使F344大鼠对AA易感，表明主动抑制在关节炎诱导阶段不起作用。这一发现在从刘易斯大鼠到F344大鼠的AA过继转移实验中得到证实。我们的数据表明F344大鼠缺乏预先存在的强大抑制作用，并表明抑制作用是在细菌攻击后产生的。抑制作用是否被推翻可能取决于所用佐剂的效力以及皮质类固醇的潜在控制作用。
