ANTIALLERGIC ACTIVITY OF LORATADINE - INHIBITION OF LEUKOTRIENE C-4 RELEASE FROM HUMAN-LEUKOCYTES

The H-1 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 C-4 (LTC(4)) 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 (Fh?LP) and Ca2+ ionophore A23187; immunoreactive (i) LTC(4) 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 mu M, exerted a dose-dependent inhibitory effect on IgE-mediated and IgE-independent histamine and iLTC(4) release. The concentrations inhibiting 50% of histamine release were 30CLM (anti-IgE), 27 mu M (FMLP) and 19 mu M (Ca2+ ionophore A23187). The concentrations inhibiting 50% of iLTC(4) release were 2.3 mu M (anti-IgE). 11 mu M (FMLP) and 1.7 mu M (Ca2+ ionophore A23187). The inhibitory activity on iLTC(4) release was optimal after preincubation for 2h at 37 degrees 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.