Mechanisms and consequences of eosinophilia in allergic diseases.

The presence of eosinophils in blood and tissues is a characteristic featur e of immediate-type hypersensitivity. Blood and tissue eosinophilia are ind uced and maintained by repeated exposures to small, non-eliciting concentra tions of allergens, and exacerbated by acute exposures to higher, eliciting concentrations of the same allergens. It has been shown that allergic eosi nophilia was induced by cytokines produced by various cell types, such as m ast cells, Th2-type lymphocytes, macrophages, epithelial and endothelial ce lls, and eosinophils themselves. The increase in the number of activated eo sinophils results from several effects of the cytokines: 1) effects on the bone marrow, mediated principally by interleukin (IL)-5, which result in pr oliferation and differentiation of eosinophil progenitors, and an increase in blood eosinophils; 2) tethering of eosinophils to vascular endothelial c ells, resulting from interactions between intercellular adhesion molecules expressed on eosinophils (IL-5 and granulocyte-macrophage colony-stimulatin g factor [GM-CSF]) and endothelial cells (IL-1, IL-4 and tumor necrosis fac tor [TNF]); 3) selective chemotaxis under the influence of IL-5, exotoxin a nd chemokines (IL-8, MIP-1 alpha, monocyte/macrophage-chemoattractant prote in [MCP-1] and regulated upon expression normal T-cell expressed and secret ed [RANTES]); 4) inhibition of apoptosis, resulting in prolonged survival o f eosinophils (IL-5); and 5) co-activation and activation of eosinophils at the site of the allergic reaction (IL-3, IL-5, eotaxin, GM-CSF). In allerg ic patients, numerous blood and tissue eosinophils are sensitized by IgE mo lecules and can be activated by allergens. Upon activation by allergens and cytokines, eosinophils produce mediators and cytokines that play an import ant role in the propagation and exacerbation of the allergic inflammation. Main eosinophil-derived cytokines are IL-3, IL-5 and GM-CSF. These cytokine s are the major factors for the survival, differentiation and activation of eosinophils, and, thus intensify the eosinophil-mediated inflammatory resp onse. Other cytokines, such as IL-1, IL-4, IL-6 and chemokines, are produce d by eosinophils, and may contribute to the allergic inflammation. In addit ion, eosinophils release potent mediators of inflammation, including leukot rienes (LTC4, LTD4) and platelet-activating factor (PAF); LTC4 is a potent bronchoconstrictor, and increases mucous production and vascular permeabili ty. PAF is a potent stimulus for chemotaxis and degranulation of eosinophil s, activates macrophages and neutrophils, and increases vascular permeabili ty. Finally, eosinophils release enzymes that are cytotoxic for epithelial cells (MBP and ECP), activate nerve endings (neurogenic inflammation), and induce activation of platelets, neutrophils, mast cells and basophils. Eosi nophilic inflammation is positively and significantly correlated with the s everity and prognosis of allergic diseases, and thus must be controlled eff iciently. Control measures include allergen eviction, anti-inflammatory tre atment (i.e., topical and/or oral corticosteroids), and hyposensitization. Studies have shown that these measures are highly efficient in reducing eos inophilic inflammation and severity of allergic diseases, especially when t hey were associated. (C) 2000 Editions scientifiques et medicales Elsevier SAS.