Serum Vitamin D and Interleukin-6 in Acute Lymphoblastic Leukemia: A Scoping Review

Abstract

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, characterized by complex interactions between immune dysregulation, inflammation, and tumor progression. Interleukin-6 (IL-6) is a key proinflammatory cytokine implicated in leukemogenesis through activation of signaling pathways such as JAK/STAT3, PI3K/Akt, and NF-κB, promoting proliferation and inhibiting apoptosis. Conversely, vitamin D is recognized for its immunomodulatory and anti-inflammatory properties, including its ability to suppress IL-6 production and modulate downstream signaling pathways. This scoping review aimed to map current evidence regarding the relationship between vitamin D and IL-6 in ALL and to explore their potential biological and clinical interactions.A simplified scoping review methodology was employed using databases including PubMed, Scopus, and ScienceDirect. Studies addressing vitamin D levels, IL-6 expression, or their association in ALL were included and synthesized descriptively. The available evidence indicates that vitamin D deficiency is highly prevalent among pediatric ALL patients, with some studies reporting rates exceeding 90%. Lower vitamin D levels are often associated with disease severity, although findings are not consistently statistically significant. IL-6 levels tend to be elevated in ALL, but clinical results are heterogeneous and influenced by multiple factors, including disease stage and treatment status. Mechanistic studies support an inverse relationship between vitamin D and IL-6; however, clinical studies, including the present analysis, do not consistently demonstrate a significant correlation. This discrepancy suggests a complex and multifactorial interaction. Further longitudinal and interventional studies are needed to clarify the clinical relevance of vitamin D–IL-6 interplay in ALL.