Enhanced peripheral leukocyte leukotriene production and bronchial hyperresponsiveness in asthmatics

Leukotrienes (LTs) are pro-inflammatory mediators that contribute to the pathophysiological features of asthma. The relationship between the amounts of 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 with 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 leukocytes obtained during exacerbations, than by those obtained during clinically controlled periods (p<0.01). In addition, there was a significant correlation between LTB4 generation by leukocytes and the degree of bronchial hyperresponsiveness to methacholine (r=-0.792, p<0.0001). These results suggest that leukotriene C4 production by leukocytes is associated with immunoglobulin E-mediated allergy and asthma exacerbations, and further that generation of leukotriene B4 is closely related to bronchial hyperresponsiveness in patients with asthma.