Nasal challenge studies with bradykinin: influence upon mediator generation.
Previous studies have shown that nasal allergen provocation leads to dose-dependent increases of inflammatory mediators, e.g. histamine, kinins, LTC4 and PGD2 in nasal lavages. To investigate further the interaction of these mediators, a titration study with intranasal bradykinin (Bk) application (maximal dose 100 nmol/nostril) and consecutive lavage were performed in eight grass-pollen-allergic patients out of season, and five controls. The nasal lavages were analysed for albumin, N-alpha-tosyl-L-arginine methyl ester (TAME) esterase activity, histamine, 9 alpha,11 beta-PGF2, and LTC4. The clinical reactions were measured with a subjective symptom score. A dose-dependent elevation of albumin was found which was significantly higher in patients with allergic and non-allergic rhinitis compared with normal volunteers. TAME-esterase activity also increased in relation to the dosage of Bk given without significant difference between the various groups. No influence on histamine, LTC4 and 9 alpha,11 beta-PGF2, release (PGD2 metabolite) was seen. Short-lasting clinical symptoms like irritation, sneezing, and obstruction were noticed after the two highest Bk dosages (10 and 100 nmol). We conclude that intranasally applied Bk induces a dose-dependent plasma leakage into the nasal cavity, which is significantly higher in patients with seasonal allergic rhinitis out of season compared to normals. Bk does not seem to affect the mast cell since histamine, LTC4 and 9 alpha,11 beta-PGF2 levels do not alter. The ability to induce relevant symptoms of rhinitis provides strong support for the hypothesis that kinins may be important mediators of inflammatory disorders of the upper airways.
Brunnée
T
T
Department of Clinical Immunology and Asthma Policlinic, Free University, Berlin, Germany.
Nigam
S
S
Kunkel
G
G
Baumgarten
C R
CR
D000328:Adult; D000418:Albumins / Q000032:analysis; D001920:Bradykinin; D004305:Dose-Response Relationship, Drug; D005260:Female; D006632:Histamine / Q000032:analysis; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D009297:Nasal Mucosa / Q000187:drug effects*; D010447:Peptide Hydrolases / Q000032:analysis; D013189:SRS-A / Q000032:analysis
D000418:Albumins; D013189:SRS-A; D006632:Histamine; D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase; D001920:Bradykinin