Intratracheal dosing with disodium cromoglycate inhibits late asthmatic response by attenuating eicosanoid production in guinea pigs.
Disodium cromoglycate is an anti-asthmatic drug that has mast cell-stabilizing effects and other anti-inflammatory effects. However, the mechanisms of its anti-inflammatory effects are unclear. In this study, we evaluated effects of disodium cromoglycate on eosinophilia, early and late asthmatic responses, and production of arachidonic acid metabolites in guinea pig lungs. Guinea pigs were alternately sensitized and challenged by exposure to mists of ovalbumin+Al(OH)(3) and ovalbumin, respectively. Disodium cromoglycate (0.5-2 mg/0.1 ml/animal) administered intratracheally before the fifth challenge dose-dependently inhibited asthmatic response, but early asthmatic response was not affected. Disodium cromoglycate at 2 mg/animal potently suppressed increases in cysteinyl leukotrienes (CysLTs) and thromboxane A(2) in the lung during late asthmatic response. Eosinophilia was slightly reduced by disodium cromoglycate. The inhibitory effect of disodium cromoglycate on late asthmatic response is apparently due to inhibition of the release of arachidonic acid metabolites, some of which may be derived from eosinophils that infiltrate the lung.
Nabe
Takeshi
T
Department of Pharmacology, Kyoto Pharmaceutical University, 5 Nakauchi, Misasagi, Yamashina, Kyoto 607-8414, Japan.
Yamamoto
Maki
M
Suga
Mikiko
M
Kohno
Shigekatsu
S
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001095:Arachidonic Acids / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004205:Cromolyn Sodium / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003545:Cysteine / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000096:biosynthesis*; D004802:Eosinophilia / Q000188:drug therapy / Q000276:immunology; D006168:Guinea Pigs; D015289:Leukotrienes / Q000096:biosynthesis; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D010047:Ovalbumin; D013928:Thromboxane A2 / Q000096:biosynthesis; D013997:Time Factors
D018927:Anti-Asthmatic Agents; D001095:Arachidonic Acids; D015777:Eicosanoids; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D013928:Thromboxane A2; D010047:Ovalbumin; D003545:Cysteine; D004205:Cromolyn Sodium