Efficacy and Safety of Low-Dose Interleukin-2 Therapy in Systemic Lupus Erythematosus: A Systematic Review.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune dysregulation, including impaired regulatory T cell (Treg) function. Low-dose interleukin-2 (Ld-IL-2) therapy has emerged as a promising approach to selectively expand Tregs and restore immune tolerance in SLE. This systematic review evaluates current evidence on the efficacy and safety of Ld-IL-2 therapy in patients with SLE. A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, the Cochrane Library, and the Virtual Health Library for studies published up to April 10, 2025. Eligible studies included randomized controlled trials, cohort studies, and open-label trials that investigated Ld-IL-2 therapy in adult patients with SLE. Data were extracted on study design, patient demographics, intervention details, clinical and immunologic outcomes, adverse events, and predictive biomarkers. Risk of bias was assessed using the Modified Downs and Black checklist. Seven studies met the inclusion criteria, encompassing a total of 517 patients with active SLE. All studies reported significant expansion of Treg populations following Ld-IL-2 treatment. Clinical outcomes consistently showed reductions in disease activity scores, such as SLEDAI and BILAG, with SRI-4 response rates ranging from 43% to 65.5%. Ld-IL-2 therapy was well tolerated, with adverse events primarily limited to mild injection-site reactions and flu-like symptoms. No serious treatment-related infections or concerns about immunogenicity were observed. Several studies identified baseline biomarkers, including low complement C3 levels, elevated PD-1^hi^ Tregs, and reduced CD4+ T cell counts, as predictors of treatment response. Ld-IL-2 therapy appears to be a safe and effective immunomodulatory treatment for patients with SLE, capable of enhancing Treg function and reducing disease activity. While current evidence is encouraging, larger multicenter randomized trials are warranted to establish standardized treatment protocols and validate predictive biomarkers for optimized patient selection.