Robinson D R, Dayer J M, Krane S M
Ann N Y Acad Sci. 1979;332:279-94. doi: 10.1111/j.1749-6632.1979.tb47122.x.
Prostaglandins, especially PGE2 and PGI2, appear to participate in the development of inflammatory reactions. While these PGs may act to promote inflammation, they may also inhibit immune reactions; this effect is largely related to stimulation of adenylate cyclase. Human rheumatoid synovial tissue explants and derived adherent synovial cells (ASC) in vitro produce large amounts of PG, primarily PGE2, which may participate in the pathogenesis of rheumatoid inflammation and promote the osteoclastic resorption of juxtaarticular bone. Rheumatoid synovial organ cultures are unusual in that they derive a significant proportion of archidonic acid substrate for the PGE2 synthesis from triglycerides, while ASC utilize primarily phospholipids. Aspirin-like, nonsteroidal anti-inflammatory drugs inhibit PGE2 synthesis by rheumatoid synovial organ cultures at concentrations similar to those achieved in plasma during therapy. Glucocorticoids are also potent inhibitors of PGE2 synthesis, and evidence from experiments with tissue labeled with 1-[14C]arachidonic acid indicates that glucocorticoids do not act to inhibit arachidonic acid release, as has been postulated for other tissues. Human peripheral blood mononuclear cells produce a factor (MCF) that regularly stimulates the production of PGE2 and collagenase from resting ASC often by over 100-fold. The MCF appears to be produced by monocytes, and its production by monocytes is enhanced by lectin-stimulated T-cells. The ability of ASC to respond to exogenous PGE2 stimulation of cAMP synthesis is inhibited or stimulated by factors that increase or decrease PGE2 levels, respectively, in the cultures. The MCF augments the responsiveness of cAMP response to PGE2 in indomethacin-treated cultures. These in vitro experiments suggest that the pathogenesis of rheumatoid inflammation involves interactions between monocyte-macrophages, lymphocytes, and synovial cells regulating the production of PGE2, cAMP, and other factors.
前列腺素，尤其是前列腺素E2（PGE2）和前列环素（PGI2），似乎参与了炎症反应的发展。虽然这些前列腺素可能起到促进炎症的作用，但它们也可能抑制免疫反应；这种作用很大程度上与腺苷酸环化酶的刺激有关。人类类风湿性滑膜组织外植体和体外培养的贴壁滑膜细胞（ASC）会产生大量的前列腺素，主要是PGE2，其可能参与类风湿性炎症的发病机制，并促进关节周围骨的破骨细胞吸收。类风湿性滑膜器官培养物的不同寻常之处在于，它们从甘油三酯中获取相当一部分用于合成PGE2的花生四烯酸底物，而ASC主要利用磷脂。阿司匹林样的非甾体抗炎药在与治疗期间血浆中达到的浓度相似时，就能抑制类风湿性滑膜器官培养物中PGE2的合成。糖皮质激素也是PGE2合成的有效抑制剂，用1-[14C]花生四烯酸标记组织的实验证据表明，糖皮质激素并不像对其他组织所假设的那样，通过抑制花生四烯酸的释放来发挥作用。人类外周血单核细胞产生一种因子（MCF），该因子通常会刺激静止的ASC产生PGE2和胶原酶，其刺激倍数常常超过100倍。MCF似乎由单核细胞产生，单核细胞产生MCF的过程会被凝集素刺激的T细胞增强。在培养物中，分别增加或降低PGE2水平的因子会抑制或刺激ASC对外源性PGE2刺激cAMP合成的反应能力。在吲哚美辛处理的培养物中，MCF增强了cAMP对PGE2反应的敏感性。这些体外实验表明，类风湿性炎症的发病机制涉及单核细胞-巨噬细胞、淋巴细胞和滑膜细胞之间的相互作用，这些细胞调节着PGE2、cAMP和其他因子的产生。
