A late cutaneous response in actively sensitized rats: a new method for evaluating the efficacy of antiallergic drugs.
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.
Shishikura
Takashi
T
Pharmaceutical Research Department, Meiji Seika Kaisha, Ltd., Yokohama, Japan. takashi_shishikura@meiji.co.jp
Shito
Keiko
K
Uchida
Mitsuhiro
M
Inaba
Tsuneyoshi
T
D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D000941:Antigens / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D004205:Cromolyn Sodium / Q000494:pharmacology; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology; D004136:Dinitrobenzenes / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004487:Edema / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control; D006241:Haptens / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D006614:Hindlimb / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects* / Q000276:immunology; D011398:Promethazine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D000631:Aminopyridines; D018926:Anti-Allergic Agents; D000941:Antigens; D004136:Dinitrobenzenes; D006241:Haptens; D011725:Pyridines; D011744:Pyrimidinones; D015363:Quinolones; D062367:ortho-Aminobenzoates; C055139:pemirolast; C048522:repirinast; D016572:Cyclosporine; D010047:Ovalbumin; C045742:amlexanox; D011398:Promethazine; C012293:tranilast; D004205:Cromolyn Sodium