Bertini R, Wang J M, Mengozzi M, Willems J, Joniau M, Van Damme J, Ghezzi P
Istituto di Ricerche Farmacologiche Mario Negri Via Eritrea, Milan, Italy.
Immunology. 1991 Jan;72(1):138-43.
Polymorphonuclear neutrophils (PMN) play a central role in the acute inflammatory response and functions associated with phagocytosis and bacterial killing, including lysosomal enzyme release and superoxide anion (O2-) generation, are also implicated in tissue injury. We have studied the modulation by chlorpromazine (CPZ) on the effects of lipopolisaccharide (LPS) in vivo in mice. Pretreatment with CPZ (4 mg/kg) and, to lesser extent, promethazine, inhibited LPS-induced hypoferraemia and lethality in mice. We have also observed that CPZ (1-15 microns) inhibited lactoferrin release by PMN in vitro, suggesting that this effect could be responsible for the inhibition of hypoferraemia. We have also evaluated the effect of CPZ on other PMN functions implicated in tissue damage and inflammation, chemotaxis and O2- production. CPZ inhibited both activities, although it had chemokinetic activity per se. These data indicate that CPZ is a modular of PMN functions in vivo and in vitro and this effect could be directly implicated in the protective action of CPZ against endotoxic shock.
多形核中性粒细胞（PMN）在急性炎症反应中起核心作用，与吞噬作用和细菌杀伤相关的功能，包括溶酶体酶释放和超氧阴离子（O2-）生成，也与组织损伤有关。我们研究了氯丙嗪（CPZ）对小鼠体内脂多糖（LPS）作用的调节。用CPZ（4mg/kg）预处理，以及在较小程度上用异丙嗪预处理，可抑制LPS诱导的小鼠低铁血症和致死率。我们还观察到CPZ（1-15微米）在体外抑制PMN释放乳铁蛋白，表明这种作用可能是抑制低铁血症的原因。我们还评估了CPZ对其他与组织损伤和炎症、趋化性和O2-产生相关的PMN功能的影响。CPZ抑制了这两种活性，尽管它本身具有化学促动活性。这些数据表明CPZ在体内和体外都是PMN功能的调节剂，这种作用可能直接与CPZ对内毒素休克的保护作用有关。
