Van Epps D E, Kutvirt S G, Potter J W
Department of Medicine, University of New Mexico, Albuquerque.
Ann Allergy. 1987 Dec;59(6 Pt 2):13-9.
IgE-mediated hypersensitivity reactions are characterized by an immediate or early-phase response within the first 30 minutes of exposure to allergen, followed by a late-phase response that begins two to six hours later. Histamine is released during both the early- and late-phase responses and inhibits a variety of neutrophil functions, including superoxide anion generation, chemotaxis, and enzyme secretion. There is some debate as to whether histamine's action on neutrophils is mediated through H1 or H2 receptors, or through a single receptor that recognizes both H1 and H2 agonists. In an effort to understand the mechanism of action of the H1-antagonist cetirizine, we studied its effects on a variety of neutrophil functions. We found that at concentrations up to 35 micrograms/mL), it does not affect superoxide anion production or degranulation. However, at higher concentrations (greater than 35 micrograms/mL), a concentration-dependent inhibition of superoxide anion production is observed. This inhibition is most apparent with responses stimulated by chemotactic factors. Limited inhibition of degranulation and chemotaxis is also seen at high concentrations, but at a level far below that seen with superoxide anion production. These studies indicate that neutrophil function is not altered by the circulating concentrations of cetirizine attained during therapy (less than 10 micrograms/mL), but may be suppressed at higher concentrations. Additional effects of cetirizine on neutrophil function, possible influences of the drug on the inflammatory response, and histamine's modulation of neutrophil function are discussed.
IgE介导的超敏反应的特点是在接触过敏原后的最初30分钟内出现即刻或早期反应，随后在两到六小时后开始出现晚期反应。组胺在早期和晚期反应中均会释放，并抑制多种中性粒细胞功能，包括超氧阴离子生成、趋化作用和酶分泌。关于组胺对中性粒细胞的作用是通过H1或H2受体介导，还是通过一种能识别H1和H2激动剂的单一受体介导，存在一些争议。为了了解H1拮抗剂西替利嗪的作用机制，我们研究了其对多种中性粒细胞功能的影响。我们发现，在浓度高达35微克/毫升时，它不影响超氧阴离子的产生或脱颗粒。然而，在更高浓度（大于35微克/毫升）时，观察到超氧阴离子产生受到浓度依赖性抑制。这种抑制在趋化因子刺激的反应中最为明显。在高浓度下也可见到脱颗粒和趋化作用的有限抑制，但程度远低于超氧阴离子产生的抑制。这些研究表明，治疗期间达到的西替利嗪循环浓度（低于10微克/毫升）不会改变中性粒细胞功能，但在更高浓度下可能会受到抑制。文中还讨论了西替利嗪对中性粒细胞功能的其他影响、该药物对炎症反应的可能影响以及组胺对中性粒细胞功能的调节作用。
