Hart P H, Jones C A, Finlay-Jones J J
Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University of South Australia, Adelaide.
J Leukoc Biol. 1993 Mar;53(3):309-19. doi: 10.1002/jlb.53.3.309.
To gain insight into the factors regulating an inflammatory response in vivo, the activities of peritoneal macrophages and the influence of the inflammatory fluids from which they were harvested were studied in continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis. Specifically, the production of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and prostaglandin E2 (PGE2) by lipopolysaccharide-stimulated human peritoneal macrophages from CAPD patients with peritonitis was examined in the presence of the inflammatory dialysates from which they were isolated. When tested at a dilution of 20%, the dialysates inhibited production of TNF-alpha, a key monokine in the orchestration of the inflammatory response. In contrast to the effect on TNF-alpha, the dialysates did not affect IL-1 beta production by stimulated macrophages. The activity inhibitory for TNF-alpha synthesis was not fully characterized, but a number of known inhibitors were shown not to be responsible for the suppressive activity. The inhibitory activity was detected in cases of noninfective peritonitis and excluded the possibility that a bacterial product was responsible. Hyperosmolality, pH, protein levels, glucose, uremic molecules, cortisol, heparin, and antibiotics were not responsible for the inhibitory activity. The activity had some similarity to the reported actions of alpha-globulins (which are acute phase proteins), PGE2, TNF-alpha soluble receptors, and IL-6, but there was no evidence for their involvement. Whether the selective suppression of TNF-alpha production is a general finding in inflammatory responses will require additional studies. This study nevertheless illustrates the potential for the host to regulate tightly the development of an excessive inflammatory response and thus to limit tissue pathology. However, it is unknown whether an appropriate host defense is compromised.
为深入了解体内调节炎症反应的因素，我们对持续性非卧床腹膜透析（CAPD）并发腹膜炎患者的腹膜巨噬细胞活性以及采集这些巨噬细胞的炎性液体的影响进行了研究。具体而言，我们检测了来自CAPD并发腹膜炎患者的脂多糖刺激的人腹膜巨噬细胞在其分离出来的炎性透析液存在的情况下肿瘤坏死因子α（TNF-α）、白细胞介素-1β（IL-1β）和前列腺素E2（PGE2）的产生。当以20%的稀释度进行测试时，透析液抑制了TNF-α的产生，TNF-α是炎症反应协调中的关键单核因子。与对TNF-α的影响相反，透析液不影响刺激的巨噬细胞产生IL-1β。对TNF-α合成具有抑制作用的活性尚未完全明确，但已表明一些已知的抑制剂与这种抑制活性无关。在非感染性腹膜炎病例中检测到了这种抑制活性，排除了细菌产物起作用的可能性。高渗性、pH值、蛋白质水平、葡萄糖、尿毒症分子、皮质醇、肝素和抗生素均与这种抑制活性无关。这种活性与报道的α球蛋白（即急性期蛋白）、PGE2、TNF-α可溶性受体和IL-6的作用有一些相似之处，但没有证据表明它们参与其中。TNF-α产生的选择性抑制是否是炎症反应中的普遍现象还需要进一步研究。然而，这项研究说明了宿主有可能严格调节过度炎症反应的发展，从而限制组织病理学变化。然而，尚不清楚适当的宿主防御是否会受到损害。
