Kelly C J, Zurier R B, Krakauer K A, Blanchard N, Neilson E G
J Clin Invest. 1987 Mar;79(3):782-9. doi: 10.1172/JCI112885.
Immunosuppressive effects of E-series prostaglandins have been demonstrated in many in vitro assays of immune responsiveness as well as in autoimmune diseases. To explore the mechanisms underlying prostaglandin E1 (PGE1)-associated immunosuppression in autoimmunity, we treated SJL mice immunized to produce immune-mediated interstitial nephritis with PGE1, PGF2 alpha, or vehicle alone. Mice receiving PGE1 treatment do not develop interstitial nephritis, nor do they display delayed-type hypersensitivity (DTH) to the immunizing renal tubular antigen preparation. The observed immunosuppression is critically dependent on PGE1 administration during the period of effector T cell induction. We therefore investigated the effect of PGE1 on the in vitro induction of DTH effector T cells reactive to renal tubular antigens (SRTA). PGE1 inhibits effector T cell induction in a dose-dependent, reversible manner, but has no inhibitory effect on fully differentiated DTH effector cells or SRTA-reactive cell lines. The PGE1 effect is indirect and mediated via nonspecific suppressor lymphokines. This suppression can be overcome by recombinant interleukin 1 (IL-1), which suggests a mechanism related to either diminished IL-1 secretion or target cell sensitivity to IL-1.
E 系列前列腺素的免疫抑制作用已在许多免疫反应性的体外试验以及自身免疫性疾病中得到证实。为了探究前列腺素 E1（PGE1）在自身免疫中相关免疫抑制的潜在机制，我们用 PGE1、前列腺素 F2α（PGF2α）或仅用赋形剂处理免疫诱导产生免疫介导性间质性肾炎的 SJL 小鼠。接受 PGE1 治疗的小鼠未发生间质性肾炎，对免疫用肾小管抗原制剂也未表现出迟发型超敏反应（DTH）。观察到的免疫抑制严重依赖于效应 T 细胞诱导期给予 PGE1。因此，我们研究了 PGE1 对体外诱导对肾小管抗原（SRTA）产生反应的 DTH 效应 T 细胞的影响。PGE1 以剂量依赖性、可逆的方式抑制效应 T 细胞的诱导，但对完全分化的 DTH 效应细胞或 SRTA 反应性细胞系没有抑制作用。PGE1 的作用是间接的，通过非特异性抑制性淋巴因子介导。这种抑制可被重组白细胞介素 1（IL-1）克服，这提示了一种与 IL-1 分泌减少或靶细胞对 IL-1 的敏感性降低相关的机制。
