ROLE OF INTERLEUKIN-5 IN ENHANCED MIGRATION OF EOSINOPHILS FROM AIRWAYS OF IMMUNIZED GUINEA-PIGS

1 Platelet activating factor (PAF), leukotriene B-4 (LTB(4)) and interleukin-5 (IL-5) are potent chemoattractants for guinea-pig eosinophils, which may be involved in eosinophil recruitment and up-regulation in allergic diseases. Eosinophils from the bronchoalveolar lavage fluid (BALF) of ovalbumin-sensitized guinea-pigs were collected 24 h after antigen provocation and migration induced by PAF, LTB(4) and rhIL-5 was studied. 2 Total BALF content and distribution of eosinophils were greater in immunized, ovalbumin-challenged guinea-pigs (5.0+/-0.8 x 10(6)/guinea-pig; 12+/-1%) than in immunized, saline-challenged animals (3.0+/-0.7 x 10(6)/guinea-pig; 7+/-1%). 3 The chemoattraction of eosinophils isolated on a metrizamide gradient was studied in micro-Boyden chambers, results being expressed as the number of migrating cells (mean+/-s.e.mean). PAF and LTB(4)-induced migration of eosinophils from immunized and OA-challenged guinea-pigs were significantly enhanced, as compared to immunized and saline-challenged animals (170+/-36 vs 35+/-9 migrating eosinophils for 10 nM PAF; 271+/-60 vs 110+/-19 for 1 nM LTB(4)). 4 The IL-5 antibody TRFR-5, in vivo, reduced eosinophil recruitment in BALF of antigen-challenged immunized animals as well as the enhanced responsiveness of eosinophils from the challenged animals, suggesting a role for IL-5 in the priming of eosinophils in vivo. 5 In contrast to TRFK-5, nedocromil sodium reduced to a similar extent eosinophil, macrophage and lymphocyte recruitment into the BALF of antigen-challenged, but failed to down-regulate the enhanced responsiveness of eosinophils from the challenged animals. 6 The increased eosinophil content in lungs from antigen-challenged guinea-pigs is thus selectively reduced by the anti-IL-5 antibody, which also attenuates the concomitant enhancement of the eosinophil responsiveness, supporting the concept that IL-5 is essential for recruitment and priming of eosinophils in vivo. In contrast, nedocromil sodium reduced non-selectively the total cell recruitment to the airways, but failed to attenuate the enhanced responsiveness of those eosinophils which migrated, indicating that its effects involve a different target.