INTERLEUKIN-4 AND INTERLEUKIN-5 AS TARGETS FOR THE INHIBITION OF EOSINOPHILIC INFLAMMATION AND ALLERGIC AIRWAYS HYPERREACTIVITY

Clinical and experimental investigations suggest that allergen-specifi c CD4+ T-cells, IgE and the cytokines IL-4 and IL-5 play central roles in initiating and sustaining an asthmatic response by regulating the recruitment and/or activation of airways mast cells and eosinophils. I L-5 plays a unique role in eosinophil development and activation and h as been strongly implicated in the aetiology of asthma. The present pa per summarizes our recent investigations on the role of these cytokine s using cytokine knockout mice and a mouse aeroallergen model. Investi gations in IL-5(-/-) mice indicate that this cytokine is critical for regulating aeroallergen-induced eosinophilia, the onset of lung damage and airways hyperreactivity during allergic airways inflammation. Whi le IL-4 and allergen-specific IgE play important roles in the regulati on of allergic disease, recent investigations in IL-4(-/-) mice sugges t that allel gic airways inflammation can occur via pathways which ope rate independently of these molecules. Activation of these IL-4 indepe ndent pathways are also intimately associated with CD4+ T-cells, IL-5 signal transduction and eosinophilic inflammation. Such IL-5 regulated pathways may also play a substantive role in the aetiology of asthma. Thus, evidence is now emerging that allergic air-ways disease is regu lated by humoral and cell mediated processes. The central role of IL-5 in both components of allergic disease highlights the requirements fo r highly specific therapeutic agents which inhibit the production or a ction of this cytokine.