Chemokines in asthma: Cooperative interaction between chemokines and IL-13

[摘要] The asthmatic response is characterized by elevated production of IgE, cytokines, chemokines, mucus hypersecretion, airway obstruction, eosinophilia, and enhanced airway hyperreactivity to spasmogens. Clinical and experimental investigations have demonstrated a strong correlation between the presence of CD4(+) T(H)2 cells, eosinophils, and disease severity, suggesting an integral role for these cells in the pathophysiology of asthma. T(H)2 cells are thought to induce asthma through the secretion of an array of cytokines (IL-4, -5, -9 -10, -13, -25) that activate inflammatory and residential effector pathways both directly and indirectly. In particular, IL-4 and IL-13 are produced at elevated levels in the asthmatic lung and are thought to be central regulators of many of the hallmark features of the disease. The potency of IL-13 in promoting airway hyperreactivity and mucus hypersecretion and the ability of IL-13 blockade to abrogate several critical aspects of experimental asthma have led to the view that this is a critical cytokine in disease pathogenesis. Extensive studies have also demonstrated a central role for chemokines in orchestrating multiple aspects of the asthmatic response. Chemokines are potent leukocyte chemoattractants, cellular activating factors, and histamine-releasing factors, which makes them particularly important in the pathogenesis of allergic inflammation. In particular, the eotaxin subfamily of chemokines and their receptor CC chemokine receptor 3 have emerged as central regulators of the asthmatic response. Recent studies have provided an integrated mechanism by which to explain the coordinate interaction between IL-13 and chemokines in the pathogenesis of asthma. In this regard, chemokines and IL-13 are attractive new therapeutic targets for the treatment of allergic disease. This article focuses on recently emerging data pertaining to the importance of chemokines, especially eotaxins, in promoting IL-13-associated allergic lung responses, as well as the potential for pharmacologically targeting these pathways. (J Allergy Clin Immunol 2003;111:227-42.).

[发布日期] 2003-02-01

[关键词] asthma;chemokine;eotaxin;IL-13