Depression of polymorphonuclear chemotaxis and T-lymphocyte proliferation following histamine inhalation in man.

Histamine, in vitro, via H2-receptor activation, exerts an inhibitory effect on polymorphonuclear (PMN) chemotaxis and T-lymphocyte proliferation. The aim of this study was to verify these histamine inhibitory effects in man. Healthy and asymptomatic asthmatic volunteers inhaled a histamine (0.1%), methacholine (0.1%) or saline aerosol for 3 min. Asthmatics were selected on the basis of low bronchial sensitivity to pharmacological agents. Blood was taken before and at different times following aerosol challenge. PMN chemotaxis was studied in vitro by the Boyden assay. T-lymphocyte proliferation was measured by counting H3-thymidine incorporation in cultured mononuclear cells. Plasma histamine was measured by a specific and sensitive radioimmunoassay. Inhalation of histamine or methacholine caused a 22-43% decrease in forced expiratory volume in one second (FEV1) in asthmatics only. In both groups, there was a transient increase of plasma histamine immediately following histamine inhalation, and 2 and 4 h later, a significant decrease of PMN chemotaxis and T-lymphocyte proliferation. Inhalation of methacholine or saline had no effect on leukocytes. Oral administration of an H2-receptor antagonist, cimetidine, before histamine inhalation, prevented the decrease of PMN chemotaxis and T-lymphocyte proliferation, whereas astemizole, an H1-antagonist, had no effect. In conclusion, histamine, at a dose commonly used for bronchial provocation tests, causes, in man, 2 and 4 h after inhalation, a depression of PMN chemotaxis (tested in vitro) and T-lymphocyte proliferation through activation of H2-receptors.