The clinical relevance of the anti‐inflammatory properties of antihistamines

The continuing worldwide increase in the incidence and prevalence of allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis (1, 2) has created considerable research interest in the mechanisms responsible for the allergic response. It is to be hoped that this research will facilitate the development of more effective and more closely targeted therapies than those presently available. Allergic in ̄ammation is characterized by an immediate response which is a consequence of IgE-dependent mediator release from mast cells or basophils. This is followed by a delayed and more prolonged in®ltration of the site of allergic in ̄ammation by leukocytes, signi®cant numbers of which are eosinophils. Both resident and in®ltrating cells are important sources of the mediators and cytokines which maintain and enhance the allergic in ̄ammatory response. The mechanisms responsible for the accumulation of proin ̄ammatory cells at tissue sites of allergic in ̄ammation are complex but probably involve selective adhesion to postcapillary venular endothelium, followed by transmigration into the tissues under the in ̄uence of chemotactic factors including lipid mediators, cytokines, and chemokines. Once in the tissues, there is an elaborate interaction between in®ltrating cells, resident cells, and the mediators and cytokines released as part of the in ̄ammatory response. Important players in these processes include cells recruited to the in ̄ammatory site, such as T cells, monocytes, eosinophils, basophils, and platelets, and resident cells including mast cells, antigen-presenting cells, epithelial cells, and endothelial cells. T cells appear to play a central role in these responses due to their capacity to release an array of cytokines which can attract and activate other proin ̄ammatory cells. A number of studies have demonstrated that T cells from the blood or bronchoalveolar lavage (BAL) ̄uid of asthmatics are activated and express mRNA encoding the cytokines interleukin (IL)-4 and IL-5 (3). IL-4 and IL-13 are responsible for the isotype switch in B cells from IgG production to that of IgE, thereby leading to sensitization of mast cells and basophils (4), while IL-5 promotes the activation and differentiation of eosinophils (5). These cytokines are produced by a subset of T helper cells termed Th2 cells which are skewed toward the production of IL-4 and IL-5. In contrast, Th1 T cells produce IL-2 and interferon (IFN)-c, which are associated with delayed-type hypersensitivity reactions (6). A T-cell response skewed toward the Th2 pathway is thought to be a prominent factor in the development of allergic in ̄ammation (7). Mast cells and epithelial cells are also important mediator producers and are potent sources of a wide range of cytokines and chemokines together with prostaglandins and leukotrienes. Normal skin and lung tissue contain few eosinophils, while, in contrast, their presence is often noted in patients with chronic allergies. For example, airway in ̄ammation in allergic asthma is characterized by in®ltration of the bronchial mucosa by large numbers of proin ̄ammatory cells, among which the eosinophil is prominent despite its being a minority constituent of circulating leukocytes (8). Examination of endobronchial biopsies or BAL ̄uid from patients with mild or moderate asthma has demonstrated a correlation between disease severity and the number of activated eosinophils. Eosinophil granule-derived mediators, Allergy 2000: 55: 53±61 Printed in UK. All rights reserved Copyright # Munksgaard 2000