Ohishi S
Department of Pharmacology, School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Yakugaku Zasshi. 2000 May;120(5):455-62.
Inflammatory signs, such as heat, redness, swelling and pain, have been described from the Greek era. In these phenomena various endogenous active substances, i.e., inflammatory mediators, could cause and manifest vascular dilatation, a vascular permeability increase and sensitization of pain receptors, etc. In order to evaluate the roles of inflammatory mediators, we have studied the time courses of inflammatory reaction along with detection of various active substances directly or indirectly in the experimental animal model of pleurisy, such as rat carrageenin-induced, and zymosan-induced pleurisy. These pleurisies showed almost similar time courses of pleural exudate accumulation and neutrophil migration. However, mediators detected in the exudates of such pleurisies were different; in carrageenin-induced pleurisy bradykinin and prostacyclin (PGI2) caused exudate formation, while zymosan-induced pleurisy showed early degradation of mast cells and activation of complements, followed by an increase in platelet activating factor (PAF). In both pleurisies TNF alpha, IL-1, IL-6 and CINC (cytokine-induced neutrophil chemoattractant) appeared similarly in the exudates to cause chemoattractant for neutrophils. TNF alpha and IL-1 could stimulate to produce IL-6 and IL-8. While prostaglandins may regulate cytokine production via a cellular cAMP-dependent mechanism. Thus one should consider the time for application of anti-inflammatory drugs, such as cyclooxygenase inhibitor, indomethacin, since it causes increases in TNF alpha and IL-1 production by reducing PGI2 and prostaglandin E2 (PGE2) levels. In conclusion, inflammatory reaction has its own automatic regulation mechanism through complex cross talks between inflammatory mediators.
炎症体征，如发热、发红、肿胀和疼痛，自希腊时代起就有记载。在这些现象中，各种内源性活性物质，即炎症介质，可引起并表现出血管扩张、血管通透性增加以及疼痛感受器敏感化等。为了评估炎症介质的作用，我们在胸膜炎的实验动物模型中，如大鼠角叉菜胶诱导的胸膜炎和酵母聚糖诱导的胸膜炎，研究了炎症反应的时间进程以及直接或间接检测各种活性物质。这些胸膜炎显示出胸膜渗出液积聚和中性粒细胞迁移的时间进程几乎相似。然而，在这些胸膜炎渗出液中检测到的介质有所不同；在角叉菜胶诱导的胸膜炎中，缓激肽和前列环素（PGI2）导致渗出液形成，而酵母聚糖诱导的胸膜炎则表现为肥大细胞早期降解和补体激活，随后血小板活化因子（PAF）增加。在两种胸膜炎中，肿瘤坏死因子α（TNFα）、白细胞介素 -1（IL -1）、白细胞介素 -6（IL -6）和细胞因子诱导的中性粒细胞趋化因子（CINC）在渗出液中出现的情况相似，可引起对中性粒细胞的趋化作用。TNFα和IL -1可刺激产生IL -6和IL -8。而前列腺素可能通过细胞cAMP依赖性机制调节细胞因子的产生。因此，人们应该考虑使用抗炎药物（如环氧合酶抑制剂吲哚美辛）的时间，因为它会通过降低PGI2和前列腺素E2（PGE2）水平导致TNFα和IL -1产生增加。总之，炎症反应通过炎症介质之间复杂的相互作用有其自身的自动调节机制。
