Enhanced peripheral leukocyte leukotriene production and bronchial hyperresponsiveness in asthmatics

Abstract

Leukotrienes (LTs) are pro-inflammatory mediators that contribute to the pathophysiological features of asthma. The relationship between the amounts of LTB 4 and LTC 4 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 LTB 4 and LTC 4 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 LTB 4 (p<0.05) and LTC 4 (p<0.01) than those of controls. The leukocytes of patients with atopic asthma generated significantly more LTC 4 than those of patients with nonatopic asthma (p<0.01). Significantly more LTC 4 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 LTB 4 generation by leukocytes and the degree of bronchial hyperresponsiveness to methacholine (r=-0.792, p<0.0001).These results suggest that leukotriene C 4 production by leukocytes is associated 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. Eur Respir J 2000; 16: 504±508.

Leukotriene Synthesis Is Increased by Transcriptional Up-Regulation of 5-Lipoxygenase, Leukotriene A4Hydrolase, and Leukotriene C4Synthase in Asthmatic Children

“…Other investigators also reported that LT production in PMNs was increased in patients with bronchial asthma (16)(17)(18)(19)(20), but the mechanisms were not clarified. Not many studies were conducted to assess possible molecular mechanisms of LT-synthesizing enzymes in asthma, especially in asthmatic children.…”

Montelukast and Churg-Strauss syndrome

“…17 In addition, it has recently been shown that the leucocytes of asthmatic patients who are not receiving oral corticosteroids produce significantly more LTB4 than those of patients treated with steroids. 18 Thus, tapering of corticosteroids in patients treated with leukotriene modifiers may result in an even greater leukotriene imbalance with a clear predominance of LTB4 activity. This is supported by the fact that no cases of CSS have so far been reported in the literature in association with the use of zileuton, the 5-lipoxygenase inhibitor that blocks the synthesis of all the leukotrienes including LTB4, even though Wechsler et al 14 referred to a patient reported to the FDA who developed a systemic eosinophilic condition in association with the use of this drug.…”

Relationship between cysteinyl leukotrienes and nitric oxide in the pathogenesis of asthma in obesity

“…Cys-LT and LTB 4 are released by granulocytes (neutrophils, eosinophils) as well as mast cells, peripheral blood monocytes and macrophages, which are involved in the pathogenesis of airway obstruction [9]. LT synthesis is increased in peripheral blood leukocytes [10,11] airway macrophages and eosinophils [12] from asthmatics compared to healthy controls. Asthma in obese subjects often manifests steroid resistance and is difficult to manage [13].…”