Modulation by Drugs of Eosinophil Recruitment Induced by Immune Challenge in the Rat

Abstract

The factors responsible for eosinophil recruitment are poorly defined, although both platelet-activating factor (PAF) and cytokines appear to be involved in regulating this process. We compared eosinophil mobilization induced by PAF or antigen injection in the peritoneal cavity of hypereosinophilic rats and the effects of the PAF antagonist BN 52021, the somatostatin analog BIM 23014, and ciclosporin A on this process. PAF induced a significant increase of both peritoneal and circulating eosinophil count. Ciclosporin A almost totally abrogated these variations, whereas BN 52021 reduced the peritoneal increase. Similarly to PAF, peritoneal antigen challenge in actively sensitized animals increased peritoneal and circulating eosinophil counts. Ciclosporin A abolished both hypereosinophilia and peritoneal eosinophil infiltration. BIM 23014 reduced the circulating eosinophils and cell infiltration. In contrast, BN 52021 primarily decreased peritoneal eosinophil recruitment, while having little effect on circulating cells. The different mechanisms of action of these drugs and the involvement of interleukin 5 in eosinophil recruitment are discussed.

Protective effects of cyclophosphamide, cyclosporin A and FK506 against antigen-induced lung eosinophilia in guinea-pigs

“…The ability of cytokines such as GM-CSF, IL-3, and tumour necrosis factoralpha (TNF-a) [24] to cause a lung eosinophilia has already been demonstrated in guinea-pigs. Other studies have shown a reduction in eosinophil infiltration of the peritoneal cavity of antigen-challenged rats [25,26] and the prevention of the late onset bronchoconstriction in antigen-challenged guinea-pigs [27], when these animals were pretreated with CsA. The present studies extend these findings and show FK506 to be a more potent compound than CsA, which agrees with in vitro results [28].…”

Somatostatin and the immune and haematopoetic system; a review

“…The hypereosinophilia in rat which can be induced by administration of cyclophosphamide or sephadex 48 h before immunization with complete Freund's adjuvant, is significantly decreased by the SS analogue BTM 23014 [63,64]. SS has been shown to enhance the formation of human leukocyte migration inhibiting factor [65].…”