Protective effects of cyclophosphamide, cyclosporin A and FK506 against antigen-induced lung eosinophilia in guinea-pigs.
A close association has been recognized between activated T cells and eosinophils in asthma, albeit circumstantial. The present study attempted to investigate this relationship in an animal model of lung eosinophilia using the new generation of T cell-selective immunosuppressants, cyclosporin A and FK506, compared with the myelotoxic immunosuppressive agent cyclophosphamide. Antigen challenge of ovalbumin-sensitized guinea-pigs resulted in a lung eosinophilia which was assessed by bronchoalveolar lavage. All three agents caused a marked suppression of lung eosinophilia at 24 h post-challenge when the compounds were administered at the time of sensitization but not when administered for 3 days before lavage. However, the lung eosinophilia at 72 h post-challenge was reduced significantly by FK506 and by cyclophosphamide, but not by cyclosporin A, when the drugs were administered for 3 days, before lavage. These results strongly suggest the involvement of T cells in antigen-induced late phase (72 h) eosinophilia in guinea-pigs but not at 24 h. The effects of cyclophosphamide were always associated with a reduction in circulating white cell counts, whereas cyclosporin A and FK506 showed no myelotoxic properties. These results suggest the potential therapeutic use of selective, non-cytotoxic immunosuppressive agents in asthma.
Norris
A A
AA
Department of Pharmacology, Fisons plc, Loughborough, UK.
Jackson
D M
DM
Eady
R P
RP
D000818:Animals; D000941:Antigens / Q000009:adverse effects; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003520:Cyclophosphamide / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use*; D006168:Guinea Pigs; D007958:Leukocyte Count; D008297:Male; D010047:Ovalbumin / Q000276:immunology; D011657:Pulmonary Eosinophilia / Q000209:etiology / Q000517:prevention & control*; D016559:Tacrolimus / Q000627:therapeutic use*
D000941:Antigens; D016572:Cyclosporine; D003520:Cyclophosphamide; D010047:Ovalbumin; D016559:Tacrolimus