Nedocromil sodium blocks the early and late phases of allergen challenge in a guinea pig model of asthma.
We developed a model of asthma in conscious guinea pigs in which both early- and late-phase reductions in specific airways conductance are demonstrable after inhalation challenge. Neutrophilia that peaks 17 hours after challenge was discovered by bronchoalveolar lavage in this model, as was eosinophilia that develops more slowly, peaking at 72 hours. Nedocromil sodium blocked both the early- and late-phase reductions in airflow, but salbutamol blocked only the early phase. Both drugs blocked the neutrophilia when given before challenge, but not when given 6 hours afterward. This suggests that the neutrophila is secondary to an intact early phase response. Nedocromil sodium, given 6 hours after challenge, reduced the eosinophilia at 72 hours but not at 17 hours. Salbutamol had no effect on the eosinophilia at either time. These results suggest that nedocromil sodium has antiinflammatory properties in the lung that are not shared by the beta 2-adrenergic stimulant drug, salbutamol.
Immunopharmacology Group, Southampton General Hospital, United Kingdom.
M K
MK
Church
P A
PA
Hutson
S T
ST
Holgate
D000336:Aerosols; D000420:Albuterol / Q000627:therapeutic use; D000485:Allergens / Q000009:adverse effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D003864:Depression, Chemical; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004804:Eosinophils / Q000187:drug effects; D006168:Guinea Pigs; D017835:Nedocromil; D009504:Neutrophils / Q000187:drug effects; D015363:Quinolones / Q000627:therapeutic use*; D013997:Time Factors
D000336:Aerosols; D000485:Allergens; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015363:Quinolones; D017835:Nedocromil; D000420:Albuterol