Cellular inflammatory responses during immediate, developing, and established late-phase allergic cutaneous reactions: effects of cetirizine.
BACKGROUND: In some previous studies, the antihistamine cetirizine has inhibited both developing (at 6 hours) and established (at 24 hours) gross late-phase skin reactions (LPR) to pollen antigens, possibly relevant to clinical drug effects. However, the effects of cetirizine at the histologic level require further definition. OBJECTIVE: To characterize cetirizine effects on gross and histologic inflammatory events from 20 minutes to 24 hours after intradermal antigen challenge in sensitive patients. METHODS: Gross and histologic responses to intradermal pollen antigen, codeine, histamine, and buffer diluent were assessed during randomized 7-day treatments with cetirizine and placebo. Accumulated neutrophils, eosinophils, activated (EG2+) eosinophils, and T lymphocytes were quantitated. The degrees of extracellular deposition of lactoferrin from neutrophils and eosinophilic cationic protein (ECP) from eosinophils were also assessed. RESULTS: During placebo treatment, wheal-and-flare responses were significantly greater to antigen at 20 minutes (p < 0.01) and induration at 6 hours (p < 0.01) at antigen challenge sites than at buffer diluent sites. During cetirizine treatment, these wheal-and-flare responses to antigen were inhibited significantly (p < 0.01) but gross LPRs were not affected. During placebo treatment, significantly more cells per high-power field were found in antigen sites than in buffer sites of neutrophils at 20 minutes (p < 0.01) and 24 hours; than in eosinophils at 20 minutes, 6 hours, and 24 hours (p < 0.01 for each); than in EG2+ cells at 20 minutes (p = 0.004), 6 hours (p = 0.001), and 24 hours (p = 0.02); and at T lymphocyte sites at 24 hours (p = 0.001). Extracellular deposition of lactoferrin and ECP was significantly greater at antigen sites than at buffer sites at 6 and 24 hours. Cetirizine treatment had no significant effect on these responses. CONCLUSION: Neutrophils, eosinophils, and T lymphocytes were persistently more common at antigen sites than at buffer sites through 24 hours. Many of these neutrophils and eosinophils were activated, releasing more lactoferrin and ECP into the extracellular dermis for at least 24 hours after antigen challenge. Cetirizine inhibited gross immediate responses to antigen, but not the gross LPR nor the cellular inflammatory responses seen in such LPR sites.