SUBSTANCE-P IS GENERATED IN-VIVO FOLLOWING NASAL CHALLENGE OF ALLERGIC INDIVIDUALS WITH BRADYKININ

Background Bradykinin, a potent inflammatory mediator, is released dur ing allergic and non-allergic rhinitis and asthma in man. Nasal bradyk inin challenge induces a dose-dependent plasma leakage into the nasal cavity and relevant symptoms of rhinitis. Objective We now report on s ubstance P generation during nasal bradykinin challenge in vivo. Metho ds The effect of locally applied bradykinin on substance P generation was studied in nine individuals, allergic to grass pollen and six non- allergic controls. In the allergies TAME-esterase activity, histamine and substance P concentrations were measured in nasal lavages and corr elated to the clinical symptoms. Results Substance P concentrations in nasal lavages increased in a dose-dependent fashion during nasal brad ykinin challenge in both groups. In the allergic group Substance P-inc reases correlated with the production of TAME-esterase activity (r = 0 .9, P < 0.05) whereas these allergic individuals did not produce any h istamine increases. The generation of substance P and the increase of TAME-esterase activity was associated with the onset of clinical sympt oms. Correlation of oedema and hypersecretion to substance P were sign ificant by linear regression analysis (r = 0.88, P < 0.005 and r = 0.8 9, P < 0.02, respectively). Bradykinin induced irritations like burnin g and itching were short-term and rare. Serial dilutions of nasal wash es produced Substance P-RIA displacement curves that paralleled the st andard curve and recovery of standard substance P that was added to na sal washes was 76 +/- 4% (mean +/- SEM), n = 8. Conclusion Bradykinin induces in vivo a dose-dependent plasma leakage into the nasal cavity without affecting mast cells, but stimulates nerve endings resulting i n the release of the neuropeptide substance P.