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

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-formyl-methionyl-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 1-50 μM, 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), 27 μM (FMLP) and l9 μM (Ca²⁺ ionophore A23187). The concentrations inhibiting 50% of iLTC₄ release were 2.3 μM (anti-IgE). 11 μM (FMLP) and 1.7 μM (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 2 h 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.