ovalbumin and tranilast

N(3',4'-dimethoxycinnamoyl) anthranilic acid (Tranilast) inhibits antibody-mediated hypersensitivity reactions, and is an effective drug for patients with bronchial asthma or allergic rhinitis. Interferon-gamma (IFN-gamma) production of ovalbumin (OA)-stimulated peripheral blood mononuclear cells (PBMCs) from hen's egg-sensitive patients with atopic dermatitis (AD) was significantly higher than those of healthy controls. Tranilast inhibited this IFN-gamma production. Moreover, interleukin-2 (IL-2) production of OA-stimulated PBMCs from hen's egg-sensitive patients with AD was also inhibited by Tranilast. Our results suggest that Tranilast can be used to the patients with food sensitive AD.

Topics: Anti-Allergic Agents; Cells, Cultured; Child, Preschool; Dermatitis, Atopic; Double-Blind Method; Food Hypersensitivity; Humans; Infant; Interferon-gamma; Interleukin-2; Lymphocytes; ortho-Aminobenzoates; Ovalbumin

Tranilast (TL) has been clinically used for the treatment of airway inflammatory diseases, although the clinical use of TL is limited because of its poor solubility and systemic side effects. To overcome these drawbacks, a novel respirable powder of TL (CSD/TL-RP) for inhalation therapy was developed using nanocrystal solid dispersion of TL (CSD/TL). Stability study on CSD/TL-RP was carried out with a focus on inhalation performance. Even after 6 months of storage at room temperature, there were no significant morphological changes in micronized particles on the surface of carrier particles as compared with that before storage. Cascade impactor analyses on CSD/TL-RP demonstrated high inhalation performance with emitted dose and fine particle fraction (FPF) of ca. 98% and 60%, respectively. Long-term storage of CSD/TL-RP resulted in only a slight decrease in FPF value (ca. 54%). Inhaled CSD/TL-RP could attenuate antigen-induced inflammatory events in rats, as evidenced by marked reduction of granulocytes in bronchoalveolar lavage fluid and inflammatory biomarkers such as eosinophil peroxidase, myeloperoxidase, and lactate dehydrogenase. These findings were consistent with decreased expression levels of mRNAs for nuclear factor-kappa B and cyclooxygenase-2, typical inflammatory mediators. Given these findings, inhalable TL formulation might be an interesting alternative to oral therapy for the treatment of asthma and other airway inflammatory diseases with sufficient dispersing stability.

Topics: Administration, Inhalation; Animals; Anti-Allergic Agents; Asthma; Biomarkers; Bronchoalveolar Lavage Fluid; Cyclooxygenase 2; Drug Compounding; Drug Stability; Dry Powder Inhalers; Granulocytes; Inflammation Mediators; Lung; Male; Nanoparticles; NF-kappa B; ortho-Aminobenzoates; Ovalbumin; Powders; Pulmonary Disease, Chronic Obstructive; Rats; Rats, Sprague-Dawley; RNA, Messenger

To test the hypothesis that stimulation of chymase secretion may contribute to plaque vulnerability and inhibition of chymase activity may enhance plaque stability.. Sixty eight-week-old male Syrian golden hamsters were randomly divided into normal control group, high-cholesterol (HC) treated group, HC+ovalbumin treated group and HC+tranilast treated group. The normal control group received a normal diet while the other three intervention groups received a high-cholesterol diet for 15 weeks. Hamsters in the HC+ovalbumin treated group underwent transcatheter pharmacological triggering at the end of week 15 after antigen sensitization and those in the HC+tranilast treated group were given tranilast intragastrically for 3 weeks before euthanasia. Serological, ultrasonographic, pathologic, immunohistochemical, and gene expression studies were performed in all animals. The total number of mast cells, proportion of degranulated mast cells and the number of extracellular granules in plaques, the apoptosis rate of vascular smooth cells, the local activities of chymase, the concentration of Ang II and the expression levels of inflammatory markers as well as plaque vulnerability index all increased significantly in HC+ovalbumin treated group, but remarkably decreased in HC+tranilast treated group, in comparison with the HC treated group. These results suggest that stimulation of chymase secretion contributes to plaque vulnerability while inhibition of chymase activity enhances plaque stability. We conclude that chymase activity provides a promising therapeutic target in the stabilization of atherosclerotic plaques.

Topics: Angiotensin II; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aorta; Apoptosis; Atherosclerosis; Body Weight; Cell Degranulation; Cholesterol; Chymases; Cricetinae; Disease Models, Animal; Disease Progression; Immunohistochemistry; Inflammation; Inflammation Mediators; Lipids; Male; Mast Cells; Mesocricetus; Microscopy, Electron, Transmission; ortho-Aminobenzoates; Ovalbumin; Peptidyl-Dipeptidase A; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Rupture; Time Factors; Ultrasonography, Doppler, Duplex

We established a new and facile model to investigate allergic mechanism and assess the effect of antiallergic compounds. Male Wistar rats were actively or passively sensitized. Active sensitization was performed by injection of both dinitrophenylated-ovalbumin (DNP-OA) and Bordetella pertussis. Nine days later, DNP-OA was injected into the right hind footpad. This antigen challenge induced a biphasic footpad swelling that consisted of an early-phase (EPR) and a late-phase response (LPR). In rats passively sensitized with rat anti-DNP-OA serum, DNP-OA induced only EPR. The EPR was suppressed by disodium cromoglycate, a mast cell stabilizer, but not by cyclosporin A, an immunosuppressant, while the LPR was suppressed by cyclosporin A. Furthermore, to investigate these two allergic responses determined by the interactions between the hapten and the carrier proteins, two distinct haptenated antigens were created. DNP-Ascaris (DNP-As) induced a marked EPR and LPR in DNP-As-sensitized rats. However, DNP-As induced only EPR in DNP-OA-sensitized rats, indicating that the usage of the same carrier protein in both sensitization and challenge was necessary for induction of LPR. These data suggest that this actively sensitization model in which EPR and LPR are functionally distinguishable should be useful for evaluating the efficacy of antiallergic compounds.

Topics: Aminopyridines; Animals; Anti-Allergic Agents; Antigens; Cromolyn Sodium; Cyclosporine; Dinitrobenzenes; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation, Preclinical; Edema; Haptens; Hindlimb; Hypersensitivity, Delayed; Male; ortho-Aminobenzoates; Ovalbumin; Passive Cutaneous Anaphylaxis; Promethazine; Pyridines; Pyrimidinones; Quinolones; Rats; Rats, Wistar

We tested the effect of Tranilast [N-(3',4'-dimethoxycinnamoyl anthranilic acid)], one of the anti-allergic agents, on the induction of interleukin 2 (IL2) responsiveness of lymphocytes from patients with bronchial asthma or hen-egg allergy following stimulation with Dermatophagoides farinae (Df) or ovalbumin (OVA), respectively. Mononuclear cells pretreated with Tranilast for 12 h failed to respond to IL2 following incubation with Df or OVA. Also Tranilast inhibited purified protein derivative (PPD)-induced IL2 responsiveness of normal lymphocytes but not the Con A-induced IL2 responsiveness of normal or allergen-sensitized lymphocytes. These results suggested that Tranilast has some immunosuppressive effect in that it inhibits antigen-induced IL2 responsiveness. Separation of potential target cells of Tranilast disclosed that antigen-presenting adherent cells were more susceptible to Tranilast than IL2-responding T-cell rich populations. Expression of HLA-DR and -DQ antigens but not DP antigens on macrophages, was significantly suppressed by treatment with Tranilast, although Tranilast scarcely decreased HLA class II antigens expression on B-cells. The suppression was overcome by interferon-gamma, which was known as an inducer for class II antigen expression. Taken together, Tranilast may suppress antigen-induced IL2 responsiveness by inhibiting HLA-DR and HLA-DQ antigens on macrophages.

Topics: Adult; Animals; Antigens, Dermatophagoides; Asthma; Child, Preschool; Food Hypersensitivity; Glycoproteins; Histamine H1 Antagonists; HLA-D Antigens; Humans; In Vitro Techniques; Infant; Interleukin-2; Lymphocytes; Macrophages; Mites; ortho-Aminobenzoates; Ovalbumin

Experimental studies have shown that N(3',4'-dimethoxycinnamoyl) anthranilic acid (Tranilast) inhibits reaginic antibody-mediated hypersensitivity reactions, and it has been demonstrated to be an effective drug for patients with bronchial asthma. On the other hand, from the nature of the cellular infiltrate seen in eczematous lesions, it appears that some form of cell-mediated immunity may be involved in addition to IgE-mediated immunity in the pathogenesis of atopic dermatitis (AD). Moreover, we have previously reported that the proliferative responses of peripheral blood mononuclear cells (PBMCs) to ovalbumin (OA) or bovine serum albumin (BSA) in children with AD who are sensitive to hen's egg or cow's milk were significantly higher than those of healthy children and hen's egg or cow's milk sensitive children with immediate symptoms. In this study, we have showed that the proliferative responses of PBMCs to OA were dose-dependently inhibited by Tranilast on patients with AD. The responding cells to OA were shown, through separation experiments, to be T cells, and the proliferative responses of T cells to OA were also dose-dependently inhibited by Tranilast. Moreover, the inhibition was thought to occur at the initial stage of the proliferative reactions. These results suggest that Tranilast can be clinically applied to patients with AD.

Topics: Antigens; Child; Child, Preschool; Dermatitis, Atopic; Food; Food Hypersensitivity; Histamine H1 Antagonists; Humans; In Vitro Techniques; Infant; Lymphocyte Activation; ortho-Aminobenzoates; Ovalbumin; Serum Albumin, Bovine

Topics: Food Hypersensitivity; Humans; Lymphocyte Activation; ortho-Aminobenzoates; Ovalbumin; Serum Albumin, Bovine

Topics: Aerosols; Animals; Antigens; Asthma; Bronchial Provocation Tests; Guinea Pigs; Injections, Intravenous; Male; ortho-Aminobenzoates; Ovalbumin; SRS-A