Novel inhibitors of pulmonary eosinophil accumulation.
|
| Abstract |
The effects of representatives of three classes of compounds were investigated on antigen-induced bronchopulmonary eosinophilia in sensitized Brown-Norway rats. Rats were sensitized by 3 weekly inhalation provocations with aerosols of ovalbumin. Twenty-four hours after a fourth weekly antigen provocation, cell populations were enumerated following bronchoalveolar lavage (BAL) in animals treated with test compounds or the appropriate vehicle. A marked eosinophil-rich influx of inflammatory cells into the bronchial lumen followed the antigen provocation in sensitized animals. Dose-related inhibitions of antigen-induced lung eosinophilia were demonstrated with: 1) glucocorticoids, given po (methylprednisolone acetate, U-8210) or by inhalation (methylprednisolone suleptanate, U-67590A); 2)the non-glucocorticoid 21-amino steroid, U-75412E, and 3) the leukotriene B4 antagonist, U-75302. The steroids methylprednisolone and U-75412E were tested for glucocorticoid activity using phorbol ester-differentiated U937 (human macrophage) cells. Methylprednisolone but not U-75412E produced a dose-dependent inhibition of lipopolysaccharide-stimulated thromboxane synthesis by the U937 cells. Leukotriene B4 antagonists and the novel 21-aminosteroid, U-75412E, which lacks glucorticoid activity, provide leads for the development of compounds which inhibit the chronic airway inflammation associated with asthma in man.
|
|---|---|
| Authors | I M Richards, S K Shields, M J Bienkowski, C J Dunn, E J Jacobsen |
| Journal | Agents and actions. Supplements (Agents Actions Suppl) Vol. 34 Pg. 359-68 ( 1991) ISSN: 0379-0363 [Print] Switzerland |
| PMID | 1665309 (Publication Type: Journal Article) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!