Evidence for Elevated Levels of Histamine, Prostaglandin D₂, and Other Bronchoconstricting Prostaglandins in the Airways of Subjects with Mild Asthma

Abstract

Histamine and certain cyclooxygenase products of arachidonic acid have been implicated as mediators of inflammation and are potent constrictors of human airways. Because asthma may represent manifestations of chronic inflammation of the airways, the levels of histamine and six prostanoid mediators were measured in airway fluids obtained by bronchoalveolar lavage (BAL) of 12 normal, 11 allergic rhinitic, and 15 asymptomatic, allergic asthmatic subjects. Simultaneous profiling of prostanoid mediators in individual samples was performed using gas chromatography-mass spectrometry. Levels of PGD2, 9 alpha,11 beta-PGF2 and PGF2 alpha were 12 to 22 times higher in asthmatic than in normal subjects (p less than 0.01), with concentrations in airway fluids of asthmatic subjects after correction for dilution of 3.8, 0.5, and 1.4 nanomolar, respectively. Levels of PGD2 and 9 alpha,11 beta-PGF2 were increased nearly tenfold in asthmatic subjects compared with those in rhinitic subjects (p less than 0.01), distinguishing the subjects with lower airway disease from those with another atopic condition. Histamine levels were increased fourfold in asthmatic subjects compared with those in normal subjects (p less than 0.001); however, similar increases were found in rhinitic subjects. We conclude that elevated levels of multiple mediators with potent bronchoconstricting activity are present in the airways of subjects with mild asthma, indicating that even mild disease is associated with evidence of airway inflammation. The interactions of bronchoconstricting mediators and airway inflammation may play important roles in the pathogenesis of asthma.

Recombinant DNase in cystic fibrosis: a protocol for targeted introduction through n-of-1 trials

“…The mast cell [17] and the eosinophil [18] are considered to play crucial roles in the production of airway inflammation, which is associated with bronchial hyperreactivity and acute episodes of asthma. The eosinophil and mast cell percentages reported in patients with chronic nonproductive cough were of the same order as those in subjects with mild classical asthma reported in the literature [19,20].…”

Histamine Induces Exocytosis and IL-6 Production from Human Lung Macrophages Through Interaction with H1 Receptors

“…The level of histamine detected in the BAL fluid of asthmatics is ϳ1-2 ng/ml (15,16). Considering the dilution of the BAL and the intimate contact between mast cells and macrophages in the airways, the concentrations of histamine surrounding lung macrophages may reach 10 Ϫ7 -10 Ϫ6 M. Our results demonstrate that these concentrations of histamine are effective to increase exocytosis and IL-6 release from macrophages.…”

Histamine regulates cytokine production in maturing dendritic cells, resulting in altered T cell polarization

“…We next tested whether histamine, either alone or in combination with LPS, has any effect on the maturation of DCs. A histamine concentration of 10 µM was used because it is within the range of concentration (2-20 µM) of histamine detected in nasal secretions and bronchoalveolar lavages from allergic patients following antigenic challenge (30)(31)(32). iDCs were stimulated with LPS in the presence or absence of histamine for 18-24 hours, and then analyzed for surface expression of maturation markers and for the ability to prime naive CD4 + T cells.…”