EFFECTS OF LORATADINE ON ANTI-IGE-INDUCED INFLAMMATION, HISTAMINE-RELEASE, AND LEUKOCYTE RECRUITMENT IN SKIN OF ATOPICS

The aim of this study was to assess the ability of the H-1-receptor an tagonist loratadine to modify anti-IgE-induced cutaneous wheal-and-fla re and late-phase reactions (WFR and LPR), as well as histamine releas e and leukocyte accumulation in skin chambers. For this purpose, 10 at opics with allergic rhinitis were entered into a double-blind crossove r study in which they received either placebo or loratadine (20 mg/day orally) for 8 days separated by a 7-day washout period. Blisters were induced on both forearms on day 7 of each treatment period, and were unroofed on day 8 and covered with plastic skin chambers. Chamber flui ds were collected during 7 h after 1-h incubation with anti-IgE or con trol IgG. Intradermal challenge with histamine and anti-IgE was perfor med at the same occasion. As compared to placebo treatment, loratadine inhibited the immediate WFRs to anti-IgE by 35% (wheal) and 65% (flar e), respectively (P<0.01), and corresponding reactions to histamine ch allenge by 50% and 70% (P<0.001), respectively. Moreover, the initial phase (0-2 h) of the LPR induced by anti-IgE was attenuated by up to a pproximate to 60% (P<0.001) during loratadine treatment. Thereafter, n o inhibition of the LPR was observed. The magnitude and time course of histamine release into skin chambers was virtually the same after lor atadine and placebo treatment, with a peak during 0-1 h and a progress ive decline during the following 2 h. Accumulation of alpha(2)-macrogl obulin, reflecting extravasation of large plasma proteins, also peaked during the first hour and was unaffected by loratadine during the 8-h observation period. Moreover, loratadine did not reduce the anti-IgE- induced recruitment of eosinophils or other subtypes of leukocytes. Al together, loratadine inhibited both the WFRs to histamine and anti-IgE and the initial phase of the IgE-mediated LPR. However, loratadine di d not express anti-inflammatory activity with respect to mast-cell med iator release or leukocyte recruitment. The latter findings are in con trast to the action of loratadine in allergic rhinitis and conjunctivi tis, suggesting that the actions of loratadine may be organ specific a nd that the effects of loratadine cannot always be extrapolated from o ne tissue to another.