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Clinical & Experimental Allergy

Antiallergic activity of loratadine: inhibition of leukotriene C4 release from human leucocytes

Authors

  • A. MIADONNA,

    Corresponding author
    1. Respiratory Allergy and Immunology Unit, Department of Internal Medicine, University of Milan, Ospedale Maggiore Policlinico, Milan, Italy
      Dr A. Miadonna Pad. Granelli, Ospedale Maggiore Polidinico, Via Sforza 35, I-20122 Milan, Italy.
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  • N. MILAZZO,

    1. Respiratory Allergy and Immunology Unit, Department of Internal Medicine, University of Milan, Ospedale Maggiore Policlinico, Milan, Italy
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  • M. LORINI,

    1. Respiratory Allergy and Immunology Unit, Department of Internal Medicine, University of Milan, Ospedale Maggiore Policlinico, Milan, Italy
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  • E. MARCHESI,

    1. Respiratory Allergy and Immunology Unit, Department of Internal Medicine, University of Milan, Ospedale Maggiore Policlinico, Milan, Italy
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  • A. TEDESCHI

    1. Respiratory Allergy and Immunology Unit, Department of Internal Medicine, University of Milan, Ospedale Maggiore Policlinico, Milan, Italy
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Dr A. Miadonna Pad. Granelli, Ospedale Maggiore Polidinico, Via Sforza 35, I-20122 Milan, Italy.

Summary

The H1 antagonist loratadine has the capacity to inhibit histamine release from human basophils. The aim of this study was to investigate whether loratadine can also inhibit leukotriene C4 (LTC4) release from human leucocytes. Basophil-enriched mononuclear cell suspensions were prepared by centrifugation of peripheral venous blood (n= 10) on discontinuous Percoll gradients. Leucocytes were stimulated with anti-IgE, N-formylmethionyl-leucyl-phenylalanine (FMLP) and Ca2+ ionophore A23187; immunoreactive (i) LTC4 release in the cell supernatant was measured by a competitive radioimmunoassay and histamine release was evaluated by an automated fluorometric technique. Loratadine, in the concentration range of 1–50μM, exerted a dose-dependent inhibitory effect on IgE-mediated and IgE-independent histamine and iLTC4 release. The concentrations inhibiting 50% of histamine release were 30 μM (anti-IgE), 27μM (FMLP) and 19μM (Ca2+ ionophore A23187). The concentrations inhibiting 50% of iLTC4 release were 2–3 μM (anti-IgE). 11 μM (FMLP) and 1.7μM (Ca2+ ionophore A23187). The inhibitory activity on iLTC4 release was optimal after preincubation for 2h at 37°C, and was no longer evident when leucocytes were stimulated 2h after cell washing. Increased extracellular Ca2+ concentrations reduced the inhibitory activity of loratadine. These results indicate that loratadine has the capacity to inhibit the release of preformed and newly generated mediators from human basophil-enriched mononuclear cell suspensions.

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