Elemental signals regulating eosinophil accumulation in the lung

In this review we identify the elemental signals that regulate eosinophil a ccumulation in the allergic lung. We show that there are two interwoven mec hanisms for the accumulation of eosinophils in pulmonary tissues and that t hese mechanisms are linked to the development of airways hyperreactivity (A HR). Interleukin-(IL)-5 plays a critical role in the expansion of eosinophi l pools in both the bone marrow and blood in response to allergen provocati on of the airways. Secondly. IL-4 and IL-13 operate within the allergic lun g to control the transmigration of eosinophils across the vascular bed into pulmonary tissues. This process exclusively promotes tissue accumulation o f eosinophils. IL-13 and IL-4 probably act by activating eosinophil-specifi c adhesion pathways and by regulating the production of IL-5 and eotaxin in the lung compartment. IL-5 and eotaxin co-operate locally in pulmonary tis sues to selectively and synergistically promote eosinophilia. Thus, IL-5 ac ts systemically to induce eosinophilia and within tissues to promote local chemotactic signals. Regulation of IL-5 and eotaxin levels within the lung by IL-4 and IL-13 allows Th2 cells to elegantly co-ordinate tissue and peri pheral eosinophilia. Whilst the inhibition of either the IL-4/IL-13 or IL-5 /eotaxin pathways resulted in the abolition of tissue eosinophils and AKR, only depletion of IL-5 and eotaxin concurrently results in marked attenuati on of pulmonary inflammation. These data highlight the importance of target ing both IL-5 and CCR3 signalling systems for the resolution of inflammatio n and AHR associated with asthma.