Role of Interleukins in Type 1 and Type 2 Diabetes

Abstract

Background: Despite distinct etiologies, type 1 diabetes (T1D) and type 2 diabetes (T2D) share chronic inflammation as a core feature. Interleukins, key immune mediators, play important yet still not fully understood roles in the development and complications of both conditions. Objective: This narrative review aims to provide a comprehensive and critical synthesis of current evidence on the role of key interleukins in T1D and T2D, highlighting their immunological functions, genetic associations, clinical correlations, and translational potential. Methods: A targeted literature search was conducted in PubMed, Google Scholar, and ScienceDirect up to January 2025, focusing on English-language clinical and experimental studies involving interleukins and their relevance to T1D and T2D. Reference lists were manually screened for additional sources. Interleukins (ILs) were reviewed individually to assess their immunobiology, disease specificity, and biomarker or therapeutic value. Findings: Pro-inflammatory cytokines such as IL-1β, IL-6, and IL-17 contribute to islet inflammation, insulin resistance, and microvascular damage in both T1D and T2D. Anti-inflammatory mediators including IL-4, IL-10, and IL-13 exhibit protective effects but vary in expression across disease stages. Less-characterized interleukins such as IL-3, IL-5, IL-9, and IL-27 demonstrate dual or context-dependent roles, particularly in shaping immune tolerance and tissue-specific complications such as nephropathy and neuropathy. Polymorphisms in IL-10 and IL-6 genes further suggest genetic contributions to interleukin dysregulation and metabolic dysfunction. Despite promising insights, translational gaps persist due to overreliance on preclinical models and limited longitudinal clinical data. Conclusions: Interleukins represent a mechanistic bridge linking immune dysregulation to metabolic derangements in both T1D and T2D. While their diagnostic and therapeutic potential is increasingly recognized, future research must address current limitations through isoform-specific targeting, context-aware interventions, and validation in large-scale, human cohorts. A unified interleukin-based framework may ultimately advance personalized strategies for diabetes prevention and treatment.

Keywords: beta-cell dysfunction; cytokines; diabetes mellitus; immunopathogenesis; inflammation; interleukins; type 1 diabetes; type 2 diabetes.

Figure 1

Role of Cytokines in Type 1 Diabetes (T1D): Cytokines secreted by immune and pancreatic cells have dual roles in the pathogenesis of T1D. On the left, regulatory cytokines (IL-10, TGF-β, IL-5, IL-4, IL-2, IL-15, IL-33, IL-35) and IL-7 produced by regulatory dendritic cells support anti-inflammatory immune responses and sustain regulatory T cells (Tregs). On the right, inflammatory cytokines (IL-6, TNF-α, IFN-α, IL-17, IL-21) promote the activation of pathogenic immune cells including Th1, Th17, CD8⁺ T cells, and NK cells. Pancreatic β cells, expressing receptors for several cytokines (IL-1, IL-4, IL-22), are particularly vulnerable to cytokine-mediated injury or regeneration. The interplay between these opposing signals influences both the initiation and progression of T1D.

Figure 2

Pathogenesis of interleukins in type 1 and type 2 diabetes. Abbreviations: IL, interleukins; T1D, type 1 diabetes; T2D, type 2 diabetes.