A Comprehensive Review of Low-Dose Interleukin-2 (IL-2) Therapy for Systemic Lupus Erythematosus: Mechanisms, Efficacy, and Clinical Applications

Cureus. 2024 Sep 5;16(9):e68748. doi: 10.7759/cureus.68748. eCollection 2024 Sep.

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that causes extensive inflammation and tissue destruction across several organs. Conventional therapies, such as nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and immunosuppressive drugs, can have serious adverse effects and are not always successful. This study looks at the possibility of low-dose interleukin-2 (IL-2) therapy as a new treatment for SLE, focusing on its mechanics, effectiveness, and clinical applicability. Low-dose IL-2 treatment selectively increases and activates regulatory T cells (Tregs), which are essential for immunological tolerance but are often lacking in SLE patients. Unlike standard medicines, which widely inhibit the immune system, low-dose IL-2 provides a more tailored approach with fewer side effects. We examined preclinical and clinical research and discovered that low-dose IL-2 dramatically enhances Treg numbers and function, lowers disease activity, and improves clinical outcomes. The primary molecular processes include the stimulation of the Janus kinase - signal transducer of activators of transcription (JAK-STAT), phosphatidylinositol 3-kinase - protein kinase B (PI3K-Akt), and mitogen‑activated protein kinase (MAPK) pathways, which enhance Treg proliferation, survival, and activity. A thorough review of clinical studies finds that low-dose IL-2 treatment is well-tolerated and effective, with fewer side effects than biologics like belimumab and rituximab. Furthermore, IL-2 therapy provides prospects for combination therapies, which may improve therapeutic success by addressing numerous components of the immune response. Despite these encouraging findings, problems such as patient response variability and the need for long-term safety data persist. Future research should prioritize refining dose regimes, discovering biomarkers for patient selection, and investigating combination medicines. Addressing these issues might solidify low-dose IL-2 treatment as a cornerstone in SLE care, providing a more accurate and individualized approach to immune regulation while considerably improving patient outcomes.

Keywords: cytokine; il-2; low dose il-2; sle; sle treatment.

Publication types

  • Review