Urinary excretion of inflammatory mediators during allergen-induced early and late phase asthmatic reactions

Background It is generally accepted that the early asthmatic response to in haled allergen is a result of IgE-mediated mast cell activation. In contras t, the underlying mechanism of the late asthmatic response is much less cle ar. Objective In order to investigate the pattern of mediator release during th e early and late asthmatic responses to allergen, measurements of the urina ry excretion of the mast cell markers 9 alpha,11 beta-PGF(2) and N-tau-meth ylhistamine were made. In addition, urinary levels of eosinophil protein X (EPX) and leukotriene E-4 (LTE4) were measured. Methods Twelve mild atopic asthmatics participated in the study. On the stu dy day, pulmonary function was recorded at baseline and for 12h after inhal ation of allergen. Urine was collected prior to challenge and thereafter at 1 h intervals. Measurements of 9 alpha,11 beta-PGF(2) and LTE4 were made w ith enzyme-immunoassay, and levels of N-tau-methylhistamine and EPX were an alysed with radioimmunoassay. Results All subjects developed both an early and late phase airway response . Within 1 h of the early peak airway response, there was a significant inc rease in the urinary concentrations (AUC/h) of 9 alpha,11 beta-PGF(2) (49.3 +/- 9.2 to 142.5 +/- 49.2; P < 0.001) N-tau-methylhistamine (10.4 +/- 1.4 to 19.5 +/- 1.4; P<0.001) and LTE4 (43.7 +/- 5.9 to 105.9 +/- 21.3; P < 0.0 01). Levels of all three mediators were also significantly increased above baseline during the LAR to 79.4 +/- 9.5 (P < 0.01), 19.8 +/- 1.9 (P < 0.001 ) and 85.6 +/- 10.4 (P < 0.001), respectively. Levels of EPX remained uncha nged during the early and late responses (39.2 +/- 10.2 to 37.5 +/- 18.5, 3 3.9 +/- 6.8). Conclusions These results indicate that mast cell activation is a feature n ot only of the early but also the late asthmatic response. Finally, increas ed LTE4 supports the contribution of the leukotrienes to airway obstruction during both phases of the asthmatic response to allergen.