Enhanced peripheral leukocyte leukotriene production and bronchial hyperresponsiveness in asthmatics

Leukotrienes (LTs) are pro-inflammatory mediators that contribute to the pa thophysiological features of asthma, The relationship between the amounts o f LTB4 and LTC4 produced by the leukocytes of asthmatic patients on the one hand and immunoglobulin E (IgE)-mediated allergy, asthma exacerbations and bronchial hyperresponsiveness was studied, Leukocytes were obtained from peripheral blood drawn from 29 atopic and 27 nonatopic asthmatics during exacerbations and clinically controlled periods , as well as from 20 control individuals, The leukocytes were stimulated wi th calcium ionophore A23187 to induce LTB4 and LTC4 production, Allergy was assessed by means of specific serum IgE or by positive skin tests, whereas bronchial hyperresponsiveness was measured by methacholine challenge. The leukocytes of the asthmatics generated significantly more LTB4 (p<0.05) and LTC4 (p<0.01) than those of controls. The leukocytes of patients with atopic asthma generated significantly more LTC4 than those of patients with nonatopic asthma (p<0.01). Significantly more LTC4 was produced by leukocy tes obtained during exacerbations, than by those obtained during clinically controlled periods (p<0.01), In addition, there was a significant correlat ion between LTB4 generation by leukocytes and the degree of bronchial hyper responsiveness to methacholine (r=-0.792, p<0.0001). These results suggest that leukotriene C-4 production by leukocytes is asso ciated with immunoglobulin E-mediated allergy and asthma exacerbations, and further that generation of leukotriene B-4 is closely related to bronchial hyperresponsiveness in patients with asthma.