PT  - JOURNAL ARTICLE
AU  - e Lapa Silva, JR
AU  - C Ruffie
AU  - BB Vargaftig
AU  - M Pretolani
TI  - Modulation of the bronchial inflammation in sensitized guinea-pigs by FK506, nedocromil sodium and dexamethasone
AID  - 10.1183/09031936.95.08081321
DP  - 1995 Aug 01
TA  - European Respiratory Journal
PG  - 1321--1327
VI  - 8
IP  - 8
4099  - http://erj.ersjournals.com/content/8/8/1321.short
4100  - http://erj.ersjournals.com/content/8/8/1321.full
SO  - Eur Respir J1995 Aug 01; 8
AB  - Guinea-pigs sensitized by a subcutaneous injection of ovalbumin in Al(OH)3 and boosted 2 weeks later exhibit marked bronchial hyperresponsiveness to various agonists and intense bronchial wall infiltration by CD4+ T-lymphocytes and eosinophils. We have compared the effect of FK506, a novel immunosuppressive agent, on the mucosal infiltration by T-cells and eosinophils with the well established drugs, nedocromil sodium and dexamethasone. Sensitized Hartley guinea-pigs were treated subcutaneously for 5 days with FK506 (100 micrograms.kg-1 daily), nedocromil sodium (30 micrograms.kg-1 daily), or dexamethasone (200 micrograms.kg-1 daily). On the day of the experiment, i.e. one week after the booster injection of antigen, the animals were killed, the lungs dissected, frozen and cryostat sections stained by immunohistochemical methods using monoclonal antibodies specific for total T-lymphocytes, CD4+ and CD8+ T-cells. Cyanide-resistant eosinophil peroxidase activity was used to stain the eosinophils. Sections were coded and positive cells enumerated in the lamina propria and adventitia of the bronchi. Sensitized and antigen-stimulated vehicle-treated guinea-pigs showed marked infiltration of the bronchial wall by CD4+ T-lymphocytes and eosinophils compared with sensitized, non-antigen stimulated animals. As compared to vehicle, FK506 or dexamethasone abolished the T-cell/eosinophil invasion in the bronchial wall, whereas nedocromil sodium was ineffective in protecting the lungs from T-lymphocyte or eosinophil infiltration. We conclude that both FK506 and dexamethasone are effective in curtailing bronchial inflammation in allergic guinea-pigs, whereas nedocromil sodium did not resolve the inflammation associated with T-lymphocytes or eosinophils.