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 H1-receptor antagonist loratadine to modify anti-IgE-induced cutaneous wheal-and-flare and late-phase reactions (WFR and LPR), as well as histamine release and leukocyte accumulation in skin chambers. For this purpose, 10 atopics with allergic rhinitis were entered into a double-blind crossover 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 fluids were collected during 7 h after 1-h incubation with anti-IgE or control IgG. Intradermal challenge with histamine and anti-IgE was performed at the same occasion. As compared to placebo treatment, loratadine inhibited the immediate WFRs to anti-IgE by 35% (wheal) and 65% (flare), respectively (P < 0.01), and corresponding reactions to histamine challenge 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 approximately 60% (P < 0.001) during loratadine treatment. Thereafter, no inhibition of the LPR was observed. The magnitude and time course of histamine release into skin chambers was virtually the same after loratadine and placebo treatment, with a peak during 0-1 h and a progressive decline during the following 2 h. Accumulation of alpha 2-macroglobulin, reflecting extravasation of large plasma proteins, also peaked during the first hour and was unaffected by loratadine during the 8-h observation period.(ABSTRACT TRUNCATED AT 250 WORDS)
Roquet
A
A
Department of Medicine, Karolinska Hospital, Stockholm, Sweden.
Raud
J
J
Halldén
G
G
van Hage-Hamsten
M
M
Hed
J
J
Hansson
L O
LO
Zetterström
O
O
Grönneberg
R
R
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D018592:Cross-Over Studies; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D017336:Loratadine / Q000627:therapeutic use*; D008297:Male; D012867:Skin / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012882:Skin Tests; D000511:alpha-Macroglobulins / Q000378:metabolism
D000888:Antibodies, Anti-Idiotypic; D000511:alpha-Macroglobulins; D007073:Immunoglobulin E; D017336:Loratadine