Thoenes G H, Sitter T, Langer K H, Bartlett R R, Schleyerbach R
Medizinische Klinik Innenstadt, University of Munich, Federal Republic of Germany.
Int J Immunopharmacol. 1989;11(8):921-9. doi: 10.1016/0192-0561(89)90114-8.
Experimental tubulointerstitial nephritis (TIN), induced in Brown Norway rats, is an autoimmune disorder in which afflicted animals display high levels of serum autoantibodies directed against antigens present on the tubular basement membrane (TBM). Serious functional damage, due to lesions of the kidney cortex, is evident 10 days after disease initiation. In an earlier study, we could show that cyclosporin A (CsA), an immunosuppressive drug, effectively prevented the onset of this illness, although it did not inhibit the formation of TBM autoantibodies. In the present study, the protective effects of CsA in autoimmune TIN was compared to those of drugs currently used to combat inflammatory ailments (i.e. prednisolone, indomethacin, naproxen, azathioprine) and a novel immunomodulating agent, leflunomide (HWA 486). Leflunomide is known to specifically inhibit the formation of T-dependent antibodies and is effective in preventing and curing animal autoimmune diseases, i.e. adjuvant arthritis disease of rats and murine lupus-like disorders. We found that not only could leflunomide inhibit TIN, but the drug-effects seemed to be more effective than those of CsA. Further, leflunomide was extremely effective in inhibiting the formation of autoantibodies to TBM, whereas CsA displayed only partial suppression. Neither prednisolone, indomethacin nor naproxen were effective in reducing the autoantibody titer, and did not offer any protection to the development of this disease. Together with the known effects on other autoimmune diseases we conclude that leflunomide is a novel immunointerventive drug protecting against several types of autoimmunity.
在棕色挪威大鼠中诱发的实验性肾小管间质性肾炎（TIN）是一种自身免疫性疾病，患病动物血清中针对肾小管基底膜（TBM）上存在的抗原的自身抗体水平很高。疾病开始10天后，由于肾皮质损伤，严重的功能损害很明显。在早期研究中，我们发现免疫抑制药物环孢素A（CsA）虽然不能抑制TBM自身抗体的形成，但能有效预防这种疾病的发生。在本研究中，将CsA对自身免疫性TIN的保护作用与目前用于治疗炎症性疾病的药物（即泼尼松龙、吲哚美辛、萘普生、硫唑嘌呤）以及一种新型免疫调节剂来氟米特（HWA 486）的保护作用进行了比较。已知来氟米特能特异性抑制T依赖性抗体的形成，对预防和治疗动物自身免疫性疾病有效，如大鼠佐剂性关节炎疾病和小鼠狼疮样疾病。我们发现，来氟米特不仅能抑制TIN，而且其药物效果似乎比CsA更有效。此外，来氟米特在抑制针对TBM的自身抗体形成方面极其有效，而CsA仅表现出部分抑制作用。泼尼松龙、吲哚美辛和萘普生在降低自身抗体滴度方面均无效，对该疾病的发展也没有提供任何保护作用。结合其对其他自身免疫性疾病的已知作用，我们得出结论，来氟米特是一种新型免疫干预药物，可预防多种自身免疫性疾病。
