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 rel evant to clinical drug effects. However, the effects of cetirizine at the histologic level require further definition. Objective: To charact erize cetirizine effects an gross and histologic inflammatory events f rom 20 minutes to 24 hours af ter intradermal antigen challenge in sen sitive patients. Methods: Gross and histologic responses to intraderma l pollen antigen, codeine, histamine, and buffer diluent were assessed during randomized 7-day treatments with cetirizine and placebo. Accum ulated neutrophils, eosinophils, activated (EG2(+)) eosinophils, and T lymphocytes were quantitated. The degrees of extracellular deposition of lactoferrin from neutrophils and eosinophilic cationic protein (EC P) from eosinophils were also assessed. Results: During placebo treatm ent, wheal-and-flare responses were significantly greater to antigen a t 20 minutes (p < 0.01) and induration at 6 hours (p < 0.01) at antige n challenge sites than at buffer diluent sites. During cetirizine trea tment, these wheal-and-hare responses to antigen were inhibited signif icantly (p < 0.01) but gross LPRs were not affected. During placebo tr eatment, significantly-more cells per high-power field were found in a ntigen 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 h ours (p < 0.01 for each); than in EG2(+) cells at 20 minutes (p = 0.00 4), 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 sit es at 6 and 24 hours. Cetirizine treatment had no significant effect o n these responses. Conclusion: Neutrophils, eosinophils, and T lymphoc ytes were persistently more common at antigen sites than at buffer sit es through 24 hours. Many of these neutrophils and eosinophils were ac tivated, releasing more lactoferrin and ECP into the extracellular der mis for at least 24 hours after antigen challenge. Cetirizine inhibite d gross immediate responses to antigen, but not the gross LPR nor the cellular inflammatory responses seen in such LPR sites.