thromboxane-b2 and Nasal-Obstruction

The aim of this study is to evaluate whether nasal airway eosinophilia is a true pathogenetic component of allergic rhinitis. We investigated the effects of TRFK5, an anti-interleukin-5 antibody, not only on leukocyte mobilization from the bone marrow, but also on the development of nasal symptoms and hyperresponsiveness in a guinea pig model of allergic rhinitis. Intranasally sensitized animals were repetitively challenged by exposure to Japanese cedar pollen as antigen. TRFK5 (100 microg/kg, i.p.) given 12 h before the final antigen challenge selectively prevented the antigen-induced eosinophilia in blood and the nasal airway, and suppressed the corresponding decrease in the number of cells in bone marrow; however, it failed to inhibit the immediate development of sneezing, early and late nasal blockage responses, goblet cell degranulation and nasal hyperresponsiveness to histamine. Furthermore, TRFK5 did not significantly affect the production of thromboxane A(2) and cysteinyl leukotrienes in the nasal airway during the late response. These results strongly suggest that while interleukin-5 is essential for eosinophil migration from the bone marrow to the nasal airway, neither interleukin-5 nor eosinophils are required for the development of the nasal symptoms and nasal hyperresponsiveness of allergic rhinitis.

Topics: Animals; Antibodies, Monoclonal; Bone Marrow Cells; Cell Degranulation; Cysteine; Eosinophils; Goblet Cells; Guinea Pigs; Histamine; Interleukin-5; Leukocytes; Leukotrienes; Male; Nasal Lavage Fluid; Nasal Mucosa; Nasal Obstruction; Nasal Provocation Tests; Rhinitis; Sneezing; Thromboxane B2

To estimate the involvement of thromboxane (Tx) A2 in the onset of nasal blockage, we examined the effect of the selective TxA2 receptor antagonist, S-1452, as well as an H1-antihistamine, diphenhydramine, on the antigen-induced increase in intranasal pressure, as an index of nasal blockage, in anesthetized guinea pigs actively sensitized by inhalation of aerosolized ovalbumin (OA). Oral administration of S-1452 or intravenous administration of diphenhydramine significantly but incompletely reduced the increase in intranasal pressure following exposure of the nasal cavity of guinea pigs to aerosolized OA. In combination, the two agents were more effective than either alone, but there was no significant difference between them. The TxB2 level was significantly elevated in nasal lavage fluid 15 and 30 min after antigen challenge. Exposure of the nasal cavity of guinea pigs to aerosolized U-46619, a TxA2 mimetic, also resulted in a marked increase in intranasal pressure, and this could be almost completely suppressed by S-1452. These findings suggest that TxA2 contributes to antigen-induced nasal blockage in guinea pigs.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Administration, Inhalation; Animals; Antigens; Bridged Bicyclo Compounds; Diphenhydramine; Fatty Acids, Monounsaturated; Guinea Pigs; Histamine; Male; Nasal Obstruction; Ovalbumin; Prostaglandin Endoperoxides, Synthetic; Thromboxane A2; Thromboxane B2

Thromboxane A2 (TxA2) seems to play an important role in bronchial constriction and hypersensitivity in asthmatics. To study the role of TxA2 in allergic rhinitis, we investigated the levels of thromboxane B2 (TxB2), a stable metabolite of TxA2, in nasal lavage fluid from patients with allergic rhinitis and from actively sensitized guinea pigs after antigen challenge by radioimmunoassay (RIA). There was a significant (p < 0.05) rise in TxB2 levels soon after antigen challenge in nasal lavage fluid from both patients (36.4 +/- 7.5 pg/ml, mean +/- SE) and models (55.6 +/- 21.8 pg/ml). In some of the patients and models, there was an dual rise in TxB2 in the 10 hours after antigen challenge. There was a significant (p < 0.03) correlation between the patients whose levels of TxB2 were re-elevated and them whose nasal airway resistance showed dual rises. These results suggest that TxA2 may contribute to the nasal obstruction in later phase in allergic rhinitis.

Topics: Adult; Animals; Antigens; Disease Models, Animal; Female; Guinea Pigs; Humans; Male; Nasal Lavage Fluid; Nasal Obstruction; Radioimmunoassay; Rhinitis, Allergic, Perennial; Thromboxane A2; Thromboxane B2