thromboxane-b2 and Rhinitis

Jia Wei Cang Er Zi San, a traditional Chinese herbal formula, has been used to treat allergic rhinitis (AR) for several centuries. However, its effect on experimental animal models and its therapeutic mechanism remain unclear.. To study the effect of Shu-Bi-Lin, a modified Jia Wei Cang Er Zi San, on an animal model of AR.. Shu-Bi-Lin was administered to the guinea pig model of AR. Meanwhile, an antihistamine-treated group for the treatment control, an ovalbumin-sensitized and untreated group for the positive control, and a sham-sensitized, sham-challenged group for the sham control were studied in parallel. Symptomatic and some pathophysiologic variables were evaluated.. Sneezing and nasal scratching after challenges were significantly ameliorated in the Shu-Bi-Lin-treated group compared with the ovalbumin-sensitized and untreated group, but rhinorrhea volume was not reduced. Shu-Bi-Lin significantly suppressed the production of IgG1 in the passive cutaneous anaphylaxis test. The thromboxane B2 level in nasal lavage fluid was significantly deceased in the Shu-Bi-Lin-treated group; however, the reduction in histamine and peptide leukotriene levels did not reach statistical significance. In addition, eosinophil infiltration and endothelial nitric oxide synthase immunoreactivity in the nasal tissues were reduced in the Shu-Bi-Lin-treated group.. Shu-Bi-Lin could alleviate the nasal symptoms of AR, and its mechanism might be related to its inhibitory effect on type I anaphylaxis reactions and eosinophil infiltration in the nasal tissues, as well as the inhibition of some mediators related to AR.

Topics: Animals; Anti-Allergic Agents; Disease Models, Animal; Drugs, Chinese Herbal; Eosinophils; Guinea Pigs; Histamine; Histamine H1 Antagonists, Non-Sedating; Immunoglobulin E; Immunoglobulin G; Leukotrienes; Loratadine; Nasal Lavage Fluid; Nasal Mucosa; Nitric Oxide Synthase Type II; Nitric Oxide Synthase Type III; Ovalbumin; Rhinitis; Sneezing; Thromboxane B2

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

A role of prostaglandins (PGs) and leukotrienes (LTs) in the pathogenesis of nasal polyps has been recently suggested. Cyclooxygenase (CO) products (thromboxane B2, PGE2 and 6-keto PGF1 alpha) and lipoxygenase (LO) products (LTB4 and LTC4) were investigated by radioimmunoassay in polyps, hypertrophic turbinates and nasal mucosa from 14 patients with non-allergic (n = 6), allergic chronic rhinitis (n = 6) and aspirin-sensitive asthma (ASA) (n = 2), who underwent polypectomy. In all tissues CO metabolite levels were found higher than LO products (P < 0.01). Nasal polyps showed a significantly lower (P < 0.05) arachidonic acid (AA) metabolism in comparison to nasal mucosa. In polyps of allergic patients significantly higher LTB4 levels (P < 0.001) and a tendency to produce higher amounts of CO products in comparison to non-allergic subjects were observed, whereas in turbinates of non-allergic patients LT levels were significantly higher in comparison to those of allergic ones (P < 0.01). In ASA patients a decreased CO/LO ratio was found supporting the hypothesis of an imbalance of AA metabolism in this syndrome. These findings seem to indicate that the occurrence of nasal polyps may represent the result of different chronic inflammatory stimuli, regulated in part by AA metabolites.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Arachidonic Acid; Asthma; Dinoprostone; Humans; Leukotriene B4; Leukotriene C4; Lipoxygenase; Middle Aged; Nasal Mucosa; Nasal Polyps; Prostaglandin-Endoperoxide Synthases; Rhinitis; Thromboxane B2; Turbinates

Arachidonic acid metabolites (AAMs) are known to be involved in inflammation. It is suggested that AAMs play an important role in the pathogenesis of nasal polyp. We have measured the levels of prostaglandin E2, 6-keto prostaglandin F1 alpha, thromboxane B2, leukotriene B4 and a mixture of leukotriene C4, D4 and E4 in both nasal polyp and maxillary sinus mucosa by radioimmunoassay. Our results showed that arachidonic acid metabolism in nasal polyps from allergic patients was more active than that from non-allergic patients. The arachidonic acid metabolism in nasal polyp was more active than in maxillary sinus mucosa among allergic patients. On the other hand, arachidonic acid metabolism in maxillary sinus mucosa was more active than that in nasal polyps among non-allergic patients. On the basis of these results, we hypothesized the causal mechanisms of nasal polyps as follows: The nasal polyp in allergic patients is caused by primary inflammation of the nasal mucosa, and sinusitis occurs secondarily. In non-allergic patients, the primary side of inflammation is located in the maxillary sinus mucosa, leading to the secondary formation of nasal polyp.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Arachidonic Acids; Child; Dinoprostone; Female; Humans; Leukotriene B4; Leukotriene E4; Male; Maxillary Sinus; Middle Aged; Mucous Membrane; Nasal Polyps; Respiratory Hypersensitivity; Rhinitis; SRS-A; Thromboxane B2

To further define the role of histamine in the nasal mucosa, we studied the possible effect of histamine provocation on the generation of prostanoids and leukotrienes, and on the induction of hyperresponsiveness to methacholine. In separate experiments, we performed nasal challenges with histamine and measured by gas chromatography negative ion mass spectrometry and by radioimmunoassay after high-performance liquid chromatography the levels of prostanoids and leukotrienes, respectively, in recovered nasal lavages 10 min after challenge. Hyperresponsiveness to methacholine was tested in both nostrils 24 h after unilateral provocation with histamine. Our data suggest that histamine induced an immediate symptomatic response, but neither led to the generation of prostaglandins or leukotrienes nor induced hyperresponsiveness to methacholine. These results differ from those achieved after antigen stimulation and emphasize the importance of mediators in addition to histamine in the allergic reaction.

Topics: Chromatography, Gas; Dose-Response Relationship, Drug; Histamine; Humans; Leukotrienes; Mass Spectrometry; Methacholine Chloride; Nasal Mucosa; Prostaglandins; Rhinitis; Thromboxane B2