Department of Biochemistry, Institute of Rheumatology, Warsaw, Poland.
Inflamm Res. 2010 Mar;59 Suppl 2:S187-8. doi: 10.1007/s00011-009-0124-5.
All known antihistaminics may affect several inflammatory events, including chemotaxis, the survival of eosinophils, and the release of chemokines and cytokines from different sources, thus highlighting the potential for modulating chronic inflammation and immune responses. The aim of the study was to examine the effect of H(1)-H(4) antihistaminic drugs in an acute model of casein-induced inflammation in rat.
Inflammation was induced by injection of a 12% solution of casein into the peritoneal cavity of male Wistar rats. The rats were treated intraperitoneally with pyrilamine maleate (10 mg/kg), cimetidine (25 mg/kg), thioperamide maleate (2 mg/kg) or ciproxifan hydrogen maleate (0.14 mg/kg) twice: 2 hours prior and 4 hours after casein administration. The level of histamine in blood and chemiluminescence of stimulated and unstimulated PMNs was measured.
The level of histamine in the casein-induced inflammation group was higher than in the control group. Treatment with pyrilamine and ciproxifan additionally increased the level of blood histamine during the inflammatory response. Peripheral blood neutrophils from rats with casein-induced inflammation tended to respond less to zymosan stimulation than the neutrophils in the controls. Selective H(1) and H(3) antagonists injected into the rats with casein-induced inflammation significantly increased the response of the neutrophils to zymosan (p < 0.01).
Histamine produced or released into the blood in the course of experimental inflammation exerts its effects on the PMN-s via stimulation of H(1) and H(3) receptors.
所有已知的抗组胺药都可能影响多种炎症事件,包括趋化作用、嗜酸性粒细胞的存活以及不同来源的趋化因子和细胞因子的释放,从而突出了调节慢性炎症和免疫反应的潜力。本研究的目的是在大鼠酪蛋白诱导的炎症急性模型中研究 H(1)-H(4)抗组胺药物的作用。
通过向雄性 Wistar 大鼠腹腔内注射 12%酪蛋白溶液诱导炎症。大鼠腹腔内给予马来酸吡拉明(10mg/kg)、西咪替丁(25mg/kg)、马来酸噻哌啶(2mg/kg)或马来酸西普罗非氢(0.14mg/kg)两次:酪蛋白给药前 2 小时和 4 小时。测量血液中组胺的水平和刺激和未刺激的 PMN 的化学发光。
酪蛋白诱导的炎症组的组胺水平高于对照组。在炎症反应期间,吡拉明和西普罗非氢的治疗还额外增加了血液中组胺的水平。来自酪蛋白诱导的炎症大鼠的外周血中性粒细胞对酵母聚糖刺激的反应性低于对照组的中性粒细胞。在诱导酪蛋白炎症的大鼠中注射的选择性 H(1)和 H(3)拮抗剂显著增加了中性粒细胞对酵母聚糖的反应(p <0.01)。
在实验性炎症过程中产生或释放到血液中的组胺通过刺激 H(1)和 H(3)受体对 PMN 发挥作用。