tranilast and Hypersensitivity

Tranilast is an orally effective anti-allergic agent evaluated for clinical activity in prevention of symptoms of allergic rhinitis. It was investigated in a randomized, pre-seasonal, and in-seasonal treatment of tranilast to test the clinical efficacy and pathophysiological changes on the onset of nasal symptoms in season. Thirty-eight patients with a history of Sugi pollinosis and positive allergic tests were treated with tranilast 300 mg daily 6 to 7 weeks before the onset of the pollen season and continuously during the season or no medication including tranilast until the onset of clinical symptoms in season. The number of sneezing and the grade of stuffiness at the onset of pollen season were inhibited significantly in pre-seasonal treatment. The number of mast cells and eosinophils in season increased compared with off-season and the threshold of nasal hypersensitivity in season decreased compared with off-season in inseasonal treatment, but not in pre-seasonal treatment. This study indicates that tranilast may have the prophylactic effect for Sugi pollinosis.

Topics: Adolescent; Adult; Aged; Eosinophils; Epithelium; Female; Histamine H1 Antagonists; Humans; Hypersensitivity; Male; Middle Aged; Nasal Mucosa; Nasal Provocation Tests; ortho-Aminobenzoates; Rhinitis, Allergic, Seasonal; Treatment Outcome

A 54-year-old woman treated with cobalt-chromium everolimus eluting stents (CoCr-EES) for her left distal circumflex and diagonal branch lesions suffered from repeated in-stent restenosis in both lesions. Neointimal proliferation occurred rapidly and almost simultaneously in the two lesions. The cause was established to be metal allergy, as determined by patch tests which were strongly positive for bare metal stents and weakly positive for CoCr-EES. Following the third successive angioplasty, we initiated treatment with prednisolone (30 mg daily) and the anti-allergic and anti-proliferative drug tranilast (300 mg daily). An elective angiogram performed 3 months later showed no evidence of in-stent restenosis in any of the stented lesions. Furthermore, the patient has remained angina-free for 15 months. The unique features of this case include: (1) near-simultaneous repeated multivessel in-stent restenosis in a patient with skin test-documented metal allergy to cobalt-chromium stents; (2) adjunctive systemic medical therapy with prednisolone and tranilast appeared to terminate the malignant restenotic cycle.

Topics: Anti-Allergic Agents; Cardiovascular Agents; Chromium Alloys; Coronary Angiography; Coronary Artery Disease; Coronary Restenosis; Drug Therapy, Combination; Drug-Eluting Stents; Everolimus; Female; Glucocorticoids; Humans; Hypersensitivity; Middle Aged; Neointima; ortho-Aminobenzoates; Patch Tests; Percutaneous Coronary Intervention; Predictive Value of Tests; Prednisolone; Prosthesis Design; Recurrence; Risk Factors; Tomography, Optical Coherence; Treatment Outcome

We examined the effects of tranilast, an anti-allergic agent, on hypersensitive inflammation and on morphology and functions of fibroblasts. In vivo, tranilast suppressed the content of collagen in granulation tissue of hypersensitive granulomatous inflammation induced by methylated bovine serum albumin (m-BSA) in rats. In culture, tranilast inhibited the TGF-beta-independent inflammatory exudate-induced stimulation of morphological changes of fibroblasts to myofibroblast-like cells and their proliferation. Collagen gel contraction by myofibroblast-like cells and fibroblasts was also inhibited by tranilast. Flow cytometric analysis revealed that tranilast suspended the cell cycle of fibroblasts at the G0/G1 phase. These results suggest that tranilast modulates the fibrosis and contraction of granulation tissue by inhibiting the growth of myofibroblast-like cells and fibroblasts.

Topics: Administration, Oral; Animals; Cell Division; Cells, Cultured; Collagen; Fibroblasts; Granuloma; Hypersensitivity; Inflammation; Male; ortho-Aminobenzoates; Rats; Rats, Sprague-Dawley; Specific Pathogen-Free Organisms

Cell suspension cultures of Luffa cylindrica, Citrullus lanatus, and related cucurbitaceous plants accumulate large quantities of bryonolic acid (3 beta-hydroxy-D:C-friedoolean-8-en-29-oic acid) [1], an acidic, pentacyclic triterpene found exclusively in the roots of the intact plants. This compound could readily be isolated from cultured cells with CHCl3 and purified simply by recrystallization. Pharmacological tests using mice demonstrated that bryonolic acid or its derivative is active against at least three types of allergies and that its activity could be increased significantly by preparing synthetic derivatives, in particular a potassium salt of its succinate ester. The biosynthesis of bryonolic acid from mevalonic acid via isomultiflorenol has been elucidated by tracer and enzymological experiments using cultured cells of watermelon both in vitro and in vivo. Furthermore, cell fractionation and electron microscopic studies on subcellular structures of luffa cells suggested that minute vesicles originating from elongated, rough endoplasmic reticulum probably play an important role in the transport of bryonolic acid which largely accumulates in the cell wall of cultured cells. The results obtained from the present study indicate that plant cell culture would be useful not only as a biological system for elucidating biosynthetic mechanisms but also as a potential source of new pharmacologically active compounds.

Topics: Animals; Arthus Reaction; Asthma; Dermatitis; Erythrocytes; Hypersensitivity; Male; Mice; Mice, Inbred Strains; Passive Cutaneous Anaphylaxis; Plants; Triterpenes

In order to confirm the mechanism of nasal secretion mediated via a nerve reflex in guinea pigs, the secretory response from the contralateral side was studied which was induced by local application of various stimulators. There was no difference in the nasal secretion between the contralateral and the stimulated sides when the secretion was induced by allergen, histamine, and capsaicin at lower doses. Methacholine caused a nasal secretion only on the stimulated side. Pretreatment with local anesthetic and ganglionic blockers blocked the secretory response bilaterally which was induced by allergen, histamine, and capsaicin. Antihistaminics also blocked the secretory response induced by allergen and histamine on both sides, but not the capsaicin-induced nasal secretion. Unilateral pretreatment with local anticholinergics prevented all secretory responses only on the stimulated side. Thus, exogenous and endogenous histamine released by the allergen-antibody reaction may stimulate histamine H1 receptors located in the sensory nerve endings as trigger, resulting in the secretory response mediated via a nerve reflex, while methacholine may act directly on nasal glands. Ketotifen and azelastine, which are chemical mediators releasing inhibitor with antihistaminergic activity, prevented the nasal secretion induced by histamine and allergen. On the other hand, disodium cromoglycate, amlexanox, and tranilast had only a slight effect on the allergen-induced nasal secretion. The secretory response on the contralateral side induced by various stimulators would be useful in the in vivo evaluation of anti-allergic drugs to demonstrate the difference in their modes of action.

Topics: Allergens; Aminopyridines; Animals; Atropine Derivatives; Bronchodilator Agents; Capsaicin; Ganglionic Blockers; Guinea Pigs; Hexamethonium; Hexamethonium Compounds; Histamine; Hypersensitivity; Lidocaine; Methacholine Chloride; Nasal Mucosa; ortho-Aminobenzoates; Parasympatholytics; Phthalazines; Pyrilamine; Reflex

Topics: Asthma; Chemotactic Factors, Eosinophil; Cromolyn Sodium; Cytokines; Depression, Chemical; Histamine; Humans; Hypersensitivity; Ketotifen; Mast Cells; ortho-Aminobenzoates; Phthalazines; SRS-A

Platelet-activating factor (PAF) is considered an important mediator in allergic and inflammatory reactions. To further investigate the role of PAF in allergic diseases, we examined the in vitro and ex vivo effect of anti-allergic drugs on PAF production by human neutrophils. Ketotifen and three Kampo medicines, which are widely used in the treatment of allergic diseases in Japan, inhibited PAF production by normal human neutrophils dose-dependently, whereas disodium chromoglycate (DSCG) and tranilast did not have any inhibitory effect. Ketotifen also suppressed ex vivo PAF production by neutrophils from healthy subjects. PAF production decreased from 40.5 +/- 5.0 units to 21.6 +/- 4.7 units after oral administration of 2 mg of ketotifen per day for one week. We also measured the concentration of lysoPAF in serum from patients with Japanese cedar pollinosis during the pollen season and followed the effect of ketotifen on lysoPAF levels in the serum from these patients. We found that the concentration of lysoPAF, a precursor and degradation product of PAF, in patients with cedar pollinosis (87.8 +/- 8.7 units) was significantly higher than in healthy subjects (54.7 +/- 7.7 units). After two weeks, lysoPAF levels decreased significantly (82.6 units to 41.3 units) only in the group treated with nasal aerosol and ketotifen. These results suggest that PAF may play a role in allergic diseases and that the clinical effects of anti-allergic drugs may at least partially be due to their anti-PAF action.

Topics: Adult; Cromolyn Sodium; Histamine H1 Antagonists; Humans; Hypersensitivity; Ketotifen; Male; Medicine, Chinese Traditional; Neutrophils; ortho-Aminobenzoates; Platelet Activating Factor; Pollen; Reference Values

The effects of a new anti-allergic agent, MY-5116: isoamyl 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c] quinoline-2-carboxylate, and its main metabolite, MY-1250: 5,6-dihydro-7,8-dimethyl-4,5-dioxo-4H-pyrano [3,2-c] quinoline-2-carboxylic acid, on 48 hr homologous PCA (PCA) in rats and the release of histamine and SRS from rat peritoneal exudate cells (PEC) induced by IgE antibody in comparison with other anti-allergic agents were investigated. Also, the effects of MY-5116 and MY-1250 on antagonistic action against histamine and LTD4 were studied. MY-5116, tranilast and ketotifen inhibited PCA at oral doses of more than 3 mg/kg, 300 mg/kg and 0.3 mg/kg, respectively. MY-1250, DSCG and tranilast inhibited significantly the release of histamine from PEC induced by the antigen-antibody reaction in a dose-dependent manner, and the values of IC50 were 4.9 X 10(-8), 4.8 X 10(-6) and 4.6 X 10(-6) g/ml, respectively. Ketotifen inhibited significantly the release of histamine at a concentration of 10(-5) g/ml, but it accelerated significantly the release of histamine from PEC at a concentration of 10(-4) g/ml. MY-1250 and tranilast suppressed the release of SRS from PEC induced by the antigen-antibody reaction. The values of IC50 of MY-1250 and tranilast were 1.5 X 10(-6) and 2.1 X 10(-6) g/ml, respectively. MY-1250 suppressed slightly the release of SRS from PEC induced by A23187. MY-5116 showed no effect on the increase of vascular permeability induced by histamine, bradykinin and serotonin in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bradykinin; Chromones; Cromolyn Sodium; Female; Guinea Pigs; Histamine H1 Antagonists; Hypersensitivity; Ketotifen; Male; Muscle, Smooth; ortho-Aminobenzoates; Passive Cutaneous Anaphylaxis; Peritoneal Cavity; Quinolines; Quinolones; Rats; Serotonin Antagonists; SRS-A

The effects of 11-oxo-11H-pyrido[2,1-b]quinazoline-2-carboxylic acid (Sm 857), a new antiallergic drug, on both bronchial asthma and active cutaneous anaphylaxis (ACA) reaction induced by Ascaris suum antigen in dogs were investigated. The airway resistance was determined using the modified Konzett-Rössler method. Sm 857 in doses of 30 and 100 mg/kg intraduodenally (i.d.) produced a remarkable inhibitory effect on the asthmatic bronchoconstriction induced by inhalation of Ascaris antigen in naturally sensitized dogs. Intravenous administration of Sm 857 (10 mg/kg) also strongly inhibited the Ascaris-induced bronchial asthma. Sm 857 had a more powerful antiasthmatic activity than tranilast. In ACA reactions, 10 dilutions of Ascaris extract and histamine were injected intradermally to dogs and each wheal provoked was determined. Sm 857 (100 and 300 mg/kg i.d.) had little or no inhibitory effect on the antigen-induced wheals, while tranilast only in a high dose (300 mg/kg i.d.) showed an inhibitory effect. Chlorpheniramine (10 mg/kg i.d.) prevented the ACA reaction completely. Sm 857 thus appeared to have no antihistaminic effect. Above findings suggest that Sm 857 may be useful for the treatment of bronchial asthma as an orally active drug, exerting its action probably through a mast cell stabilizing effect.

Topics: Animals; Antigens, Helminth; Ascaris; Asthma; Bronchi; Dogs; Dose-Response Relationship, Drug; Hypersensitivity; Immunization; Male; ortho-Aminobenzoates; Passive Cutaneous Anaphylaxis; Quinazolines; Respiration

Slow-reacting substance of anaphylaxis (SRS-A) is an important factor mediating bronchoconstriction in asthma. We developed a guinea pig model for SRS-A-mediated bronchoconstriction induced by antigen inhalation. Using this model, we investigated the effect of N-(3', 4'-dimethoxycinnamoyl) anthranilic acid (N-5'), a new anti-allergic drug, on the bronchoconstriction. FPL 55712 inhibited most of the bronchoconstriction induced by antigen inhalation. N-5' inhibited the antigen-induced bronchoconstriction in a dose-dependent fashion. Intraperitoneal administration of 200 mg/kg N-5' was effective for 40 min after antigen inhalation, while the effect of 60 mg/kg lasted only 7 min. On the other hand, 200 mg/kg N-5' showed no inhibitory effect on the bronchoconstriction caused by direct inhalation of leukotriene C4, a component of SRS-A. These findings indicate that one of the anti-allergic actions of N-5' is due to inhibition of synthesis and/or release of SRS-A.

Topics: Animals; Antigens; Bronchi; Bronchodilator Agents; Guinea Pigs; Hypersensitivity; ortho-Aminobenzoates; SRS-A