Shih W, Hines W H, Neilson E G
Department of Medicine, University of Pennsylvania, Philadelphia.
Kidney Int. 1988 Jun;33(6):1113-8. doi: 10.1038/ki.1988.119.
We examined the effect of daily cyclosporin A administration on the development and extent of tubulointerstitial nephritis produced in rats immunized with tubular basement membranes in adjuvant. Six mg/kg/day of cyclosporin A, given from the time of immunization, completely blocked the development of interstitial lesions and renal insufficiency. The administration of cyclosporin A after the development of interstitial nephritis also arrested the progression of the histological lesions. Both T cell-mediated and humoral immunity were markedly reduced by the administration of cyclosporin A, as evidenced by the near absence of delayed-type hypersensitivity responses and by the reduced production of anti-tubular basement membrane antibodies. Cell admixture experiments indicated that impairment of the delayed-type hypersensitivity response to tubular antigen was probably not the result of active suppression, and suggested that the protective effect of cyclosporin A might be secondary to its direct inhibitory action on the activation of nephritogenic T and B cells. Finally, the treatment of control rats with cyclosporin A, in the doses used, did not produce any detectable kidney damage nor did it impair renal function. We conclude that cyclosporin A can be an effective prophylactic and therapeutic agent in autoimmune interstitial nephritis in rats.
我们研究了每日给予环孢素A对用佐剂中的肾小管基底膜免疫的大鼠所产生的肾小管间质性肾炎的发展及程度的影响。从免疫时起给予6毫克/千克/天的环孢素A，可完全阻止间质病变和肾功能不全的发展。在间质性肾炎发展后给予环孢素A也可阻止组织学病变的进展。给予环孢素A后，T细胞介导的免疫和体液免疫均明显降低，这表现为几乎没有迟发型超敏反应以及抗肾小管基底膜抗体产生减少。细胞混合实验表明，对肾小管抗原的迟发型超敏反应受损可能不是主动抑制的结果，并提示环孢素A的保护作用可能继发于其对致肾炎T细胞和B细胞活化的直接抑制作用。最后，以所用剂量用环孢素A治疗对照大鼠，未产生任何可检测到的肾损伤，也未损害肾功能。我们得出结论，环孢素A在大鼠自身免疫性间质性肾炎中可以是一种有效的预防和治疗药物。
