Evidence that 13–14 di-hydro, 15-keto prostaglandin D₂-induced airway eosinophilia in guinea-pigs is independent of interleukin-5

Abstract.

Objective and design:

Prostaglandin D₂ (PGD₂) has been shown to cause eosinophil, basophil and Th2 cell chemotaxis in vitro and in vivo through an action on the prostaglandin CRTH2 receptor. In the present study, the dependence of PGD₂-induced eosinophil accumulation in vivo on interleukin-5 (IL-5) blood eosinophilia was investigated.

Materials:

Guinea-pigs were exposed to aerosols of 13,14dihydro 15-keto PGD₂ (DK-PGD₂) or platelet activating factor (PAF) and the eosinophil content of the bronchoalveolar lavage fluid or blood determined. In some experiments, DK-PGD₂ was administered systemically and eosinophilia measured.

Results:

Aerosols of DK-PGD₂ caused eosinophil accumulation in the lungs 24h after exposure. DK-PGD₂ (10 μg.ml^-1) -induced airway eosinophilia was inhibited when animals were treated with the CRTH2 receptor antagonist ramatroban. 1–4h after exposure to DK-PGD₂ a significant decrease in blood eosinophil count was measured. The anti-IL-5 antibody TRFK-5 had no inhibitory effect of DK-PGD₂-induced airway eosinophilia, but abolished airway eosinophilia induced by exposure of guinea-pigs to aerosols of PAF. Intracardiac injection of DK-PGD₂ induced a dose-related increase in blood eosinophil numbers.

Conclusions:

It is concluded that, in the guinea-pig, DKPGD₂-induced airway eosinophilia is mediated by an action on prostaglandin CRTH2 receptors and that this response appears to be independent of IL-5.