Interleukin-18 in Allergic Diseases-Pathogenesis and Therapeutic Targeting

Allergic diseases, including pathologies such as allergic rhinitis, asthma, atopic dermatitis, and food allergies, are fundamentally driven by aberrant immunoglobulin E (IgE) production and pronounced T helper 2 (Th2) cell responses. The escalating global prevalence of these conditions represents a substantial public health challenge, stimulating intensive research into novel therapeutic vulnerabilities. Interleukin-18 (IL-18), a pleiotropic cytokine operating at the interface of innate and adaptive immunity, has emerged as a key modulator in this context. While classically associated with augmenting interferon-γ (IFN-γ) production by Th1 cells, IL-18 paradoxically promotes the maturation and functional potentiation of mast cells and basophils, particularly in synergy with IL-2, thereby contributing mechanistically to the immunopathology of allergic inflammation. The bioactivity of IL-18 is contingent upon proteolytic processing, and the precise molecular pathways through which it orchestrates allergic responses remain under active investigation. This review comprehensively synthesizes the current understanding of IL-18 biology, detailing its cellular origins, activation mechanisms, and intracellular signaling cascades. Furthermore, we critically evaluate the multifaceted impact of IL-18 on key immune cell subsets involved in allergic hypersensitivity and discuss the rationale and potential for therapeutic interventions targeting the IL-18 axis in the management of allergic diseases.