The Crosstalk Between Protective and Detrimental Interleukin (IL)-1 Family of Cytokines in Alzheimer's Disease

Alzheimer's disease (AD) is a long-term, progressive, degenerative disorder. One of the most important pathological characteristics of AD is the deposition of β-amyliod (Aβ) peptide, which initiates a spectrum of cerebral neuroinflammation. Vascular changes also play an important role in the pathophysiology of the disease. Cytokines, secreted by immune cells, can facilitate cell-to-cell signaling and influence the functions of the central nervous system (CNS). These important mediators of the immune system, which are known to orchestrate various molecular and cellular mechanisms in both physiological and pathological situations, can be upregulated or downregulated, leading to a complex crosstalk with numerous receptors mediating pro-inflammatory and/or anti-inflammatory actions. In particular, the interleukin (IL)-1 family of cytokines has been implicated to significantly correlate with AD pathogenesis among other cytokines in the CNS. The IL-1 family of cytokines is essential in both the innate and adaptive immune responses. This pleiotropic family of cytokines includes IL-1α, IL-1β, IL-1 receptor antagonist (RA), IL-18, IL-33, IL-36α, IL-36β, IL-36γ, IL-36RA, IL-37, and IL-38. Recent studies have demonstrated that the upregulation of pro-inflammatory cytokines, such as IL-1α and IL-1β, or the downregulation of anti-inflammatory mediators, exerts multifaceted influences on both neurodegeneration and neuroprotection. The lack of effective treatment for AD necessitates the search for new drugs that target several processes in the disease's pathology. This review aims to give a comprehensive overview of the emerging roles of the IL-1 family of cytokines in AD pathology and to explain their perspectives on introducing novel strategies for effective therapeutic/neuropsychiatric management of AD in clinical settings by discussing both the pathogenic and protective roles of these cytokines.