Do nasal mast cells release histamine on stimulation with substance P in allergic rhinitis?
The effects of nasal administration of increasing doses of exogenous substance P have been studied in patients with allergic rhinitis treated with placebo or with the H1 antagonist cetirizine (10 mg twice daily for 3 days). Responses to substance P were assessed by posterior rhinomanometry (measuring nasal airway resistance) and by measure of histamine, protein and albumin production and cell recovery in nasal lavage fluids before and after challenge. Substance P induced a dose-dependent increase in nasal airway resistance which was similar after treatment with either cetirizine or placebo (maximal increase in nasal airway resistance was 4.2-fold greater than the baseline with the placebo and 4.7-fold greater than the baseline with cetirizine). No histamine release was observed. Similar increases in protein and albumin production were observed after stimulation with substance P along with the placebo (protein: from 0.35 +/- 0.11 to 3.31 +/- 0.62 mg and albumin: from 0.09 +/- 0.04 to 2.08 +/- 0.39 mg) and when combined with cetirizine treatment (proteins: from 0.42 +/- 0.09 to 3.62 +/- 0.77 and albumin: from 0.17 +/- 0.04 to 2.19 +/- 0.51 mg). After stimulation with substance P, percentages of neutrophils recovered in nasal fluids increased from 26.2 +/- 11.5 to 54.5 +/- 9.5 with the placebo and from 35.5 +/- 11.0 to 53.6 +/- 9.5 with cetirizine. Eosinophils were inconsistently found after substance P stimulation during both treatments. In conclusion, nasal response to substance P is not modified by cetirizine which suggests that the effect of substance P is not secondary to histamine release in the nose in man.
Braunstein
G
G
Laboratoire de physiologie respiratoire, UFR Cochin-Port-Royal, Paris, France.
Buvry
A
A
Lacronique
J
J
Desjardins
N
N
Frossard
N
N
D000328:Adult; D000403:Airway Resistance / Q000502:physiology; D017332:Cetirizine / Q000627:therapeutic use*; D002634:Chemotaxis, Leukocyte; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006636:Histamine Release; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D009297:Nasal Mucosa / Q000276:immunology* / Q000473:pathology; D009299:Nasal Provocation Tests; D012221:Rhinitis, Allergic, Perennial / Q000188:drug therapy / Q000276:immunology*; D013373:Substance P / Q000494:pharmacology*
D013373:Substance P; D017332:Cetirizine