The IL-1R/TLR family has been receiving considerable attention as potential regulators of inflammation through their ability to act as either activators or suppressors of inflammation. Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, allergic inflammation, elevated serum total, allergen-specific IgE levels, and increased Th2 cytokine production. The discovery that the IL-1RI–IL-1 and ST2–IL-33 pathways are crucial for allergic inflammation has raised interest in these receptors as potential targets for developing new therapeutic strategies for bronchial asthma. This paper discusses the current use of neutralizing mAb or soluble receptor constructs to deplete cytokines, the use of neutralizing mAb or recombinant receptor antagonists to block cytokine receptors, and gene therapy from experimental studies in asthma. Targeting IL-1RI–IL-1 as well as ST2–IL-33 pathways may promise a disease-modifying approach in the future. 1. Introduction Asthma is characterized by allergic inflammation of the airways with local infiltration of eosinophils, mast cells, and activated T helper lymphocytes [1]. The initial immune response responsible for this is the generation of allergen-specific CD4+ T helper-2 cells (Th2) that produce Th2 cytokines (IL-4, IL-5, IL-9, and IL-13), but not T helper-1 (Th1) cytokines (IL-2, IL-12, and interferon- [IFN- ]). Overwhelming evidence in literature supports the concept that allergic inflammation is driven by an imbalance between Th1 and Th2 cytokines, favoring the Th2 immune response [1]. IL-4, together with IL-13, is required for Th2-cell development and is intimately involved in the regulation of immunoglobulin E (IgE) production by sensitized allergen-specific B cells, which is a fundamental mechanism in the pathogenesis of allergic asthma [2]. IL-5 is the principal cytokine involved in eosinophil growth, maturation, differentiation, survival, and activation [3, 4]. Cross-linking of allergen-specific IgE on mast cells and the activation of T cells and eosinophils during subsequent encounters with antigens stimulates the release of various preformed and newlysynthesized products, including histamines, cytokines, and chemokines. Together, these lead to characteristic airway changes that contribute to airway obstruction, airway hyperresponsiveness (AHR), goblet cell metaplasia, mucus overproduction, mucosal edema, and airway remodeling [5]. Pulmonary allergic inflammation can be induced in small rodents, such as BALB/c mice, is widely used as an experimental model for human asthma, and is central
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