INFLAMMATION AND THE ALLERGIC RESPONSE

The atopic diseases-allergic rhinitis, asthma, and atopic dermatitis-are chronic inflammatory diseases characterized by an exacerbating and remitting course and can only rarely be associated causally with allergen exposure. The challenge to ascribe an allergic basis to these diseases is derived from the apparent inability to reconcile these chronic inflammatory features with a process thought to be initiated by the rapid release of mediators after the interaction of allergen with IgE-coated mast cells. The traditional understanding has been that mast cell activation results in the release of a series of preformed and rapidly synthesized substances that mediate the immediate onset of vasodilatation, vascular leakage, smooth muscle contraction, and irritant nerve receptor stimulation. These mediators, however, are rapidly degraded and are not thought to be associated with a significant inflammatory component. Recent studies, however, have established that the interaction of allergen with the immune system is, in fact, far more complex. In addition to mast cell activation, allergen can interact with and activate T-lymphocytes and mononuclear phagocytic cells, leading to the secretion of cytokines and other inflammatory substances. Furthermore, the interaction of allergen with the mast cell may be far more complex, with the potential to stimulate the delayed release of newly synthesized cytokines. The interaction of allergen with the immune system also promotes the secondary release of inflammatory neuropeptides. Thus, the known spectrum of mediators released after allergen exposure has vastly been expanded. These include numerous still uncharacterized chemotactic and activating peptides; eicosanoids such as 5-HETE, 12-HETE, and leukotriene B4; platelet-activating factor; several proteases; neuropeptides; and, most importantly, the cytokines. These mediators recruit and activate neutrophils, monocytes, basophils, and eosinophils, attract additional lymphocytes and mononuclear phagocytic cells, and induce mast cell proliferation with further mast cell degranulation. A vicious cycle subsequently develops, with further inflammation and tissue destruction. Thus, the interaction of allergen with the immune system has become a complex cascade capable of producing the chronic inflammatory changes characteristic of allergic diseases.