Agents Actions, Special Conference Issue (1992) 0065-4299/92/02C311-04 $1.50+0.20/0 9 1992 Birkh/iuser Verlag, Basel Inhibition of histamine release from human FceRI + cells by nimesulide O. Marino, V. Casolaro, S. Meliota, C. Stellato, G. Guidi 1 and G. Marone 2 University of Naples Federico II, Second School of Medicine, Division of Clinical Immunology, Via Sergio Pansini 5, 80131 Naples, Italy Abstract We have previously demonstrated that pharmacological concentrations of non-steroidal anti-inflamma- tory drugs (NSAID) such as indomethacin, acetylsalicylic acid, and meclofenamic acid enhance IgE- mediated histamine release (HR) from human basophils. We have now examined the effects of nimesulide (NIM), a new NSAID, on mediator release from human basophils. Preincubation (10 rain at 37~ of basophils with pharmacological concentrations (10-6-10-3M) of NIM resulted in a concentration- dependent decrease of H R induced by anti-IgE, the Ca 2 +-ionophore A23187 and the formylated tripeptide f-Met-Leu-Phe (FMLP). Maximal inhibition of anti-IgE-induced HR was achieved after preincubation with 10-4MNIM and ranged between 14.5% and 44.5% (mean_+SEM, 29.7_+4.5%). The drug had a marked inhibitory effect on HR from basophils induced by A23187 (80.6_+ 5.5%), FMLP (63.5_+ 10.3%), 12-O-tetradecanoyl-phorbol-13-acetate (57.0+ 8.7%) and bryostatin 1 (65.7-+ 7.6%). NIM also inhibited the IgE-mediated synthesis of peptide leukotriene C4 from basophils. Introduction Pharmacological concentrations of non-steroidal anti-inflammatory drugs (NSAID), such as indo- methacin (IND), acetylsalicylic acid (ASA), and meclofenamic acid (MCA), enhance IgE-mediated HR from human peripheral blood basophils [1]. This property is not limited to the three drugs mentioned, but appears to be a general property of all NSAID [2], and there is a significant correlation between the potency of NSAID to enhance IgE- mediated HR and their capacity to inhibit the cyclo-oxygenase pathway [3]. i Present address: LPB Istituto Farmaceutico, Milan, Italy. 2 Author for correspondence. Nimesulide (NIM) is a new NSAID which inhibits in vitro the respiratory burst of human polymor- phonuclear cells without affecting their phagocytic or chemotactic responsiveness [4]. NIM also in- hibits the immunological release of histamine in guinea pigs [5]. In addition, there is preliminary evidence that NIM is well tolerated in asthmatic patients intolerant to other NSAID [6]. Despite the remarkable anti-inflammatory proper- ties of NIM, its effects on human Fc~RI + cells (basophils and mast cells) have not yet been fully investigated. We therefore compared the effects of NIM and of the NSAID IND, ASA and MCA on HR from human basophils. We have also studied the effects of NIM on the IgE-mediated release of peptide leukotriene C4 (LTC4) from basophils.