Low-dose IL-2 therapy in autoimmune diseases: An update review

Int Rev Immunol. 2024 May;43(3):113-137. doi: 10.1080/08830185.2023.2274574. Epub 2023 Oct 26.

Abstract

Regulatory T (Treg) cells are essential for maintaining self-immune tolerance. Reduced numbers or functions of Treg cells have been involved in the pathogenesis of various autoimmune diseases and allograft rejection. Therefore, the approaches that increase the pool or suppressive function of Treg cells in vivo could be a general strategy to treat different autoimmune diseases and allograft rejection. Interleukin-2 (IL-2) is essential for the development, survival, maintenance, and function of Treg cells, constitutively expressing the high-affinity receptor of IL-2 and sensitive response to IL-2 in vivo. And low-dose IL-2 therapy in vivo could restore the imbalance between autoimmune response and self-tolerance toward self-tolerance via promoting Treg cell expansion and inhibiting follicular helper T (Tfh) and IL-17-producing helper T (Th17) cell differentiation. Currently, low-dose IL-2 treatment is receiving extensive attention in autoimmune disease and transplantation treatment. In this review, we summarize the biology of IL-2/IL-2 receptor, the mechanisms of low-dose IL-2 therapy in autoimmune diseases, the application in the progress of different autoimmune diseases, including Systemic Lupus Erythematosus (SLE), Type 1 Diabetes (T1D), Rheumatoid Arthritis (RA), Autoimmune Hepatitis (AIH), Alopecia Areata (AA), Immune Thrombocytopenia (ITP) and Chronic graft-versus-host-disease (GVHD). We also discuss the future directions to optimize low-dose IL-2 treatments.

Keywords: Alopecia areata; autoimmune hepatitis; chronic graft-versus-host-disease; immune thrombocytopenia; interleukin-2; rheumatoid arthritis; systemic lupus erythematosus; type 1 diabetes.

Plain language summary

Low-dose interleukin-2 (IL-2) is a potential treatment for autoimmune diseases. IL-2 is a protein that helps regulate the immune system, and low doses of it can activate regulatory T cells (Tregs), which help control the immune response. This can be beneficial in autoimmune diseases where the immune system attacks healthy tissues. We discuss several clinical trials that have investigated the effectiveness of low-dose IL-2 in treating autoimmune diseases. These trials have shown promising results, with some patients experiencing improvements in symptoms and disease progression. However, more research is needed to determine the safety and effectiveness of low-dose IL-2 as a treatment for autoimmune diseases. IL-2 can also activate other immune cells, which may cause unwanted side effects. Therefore, careful monitoring and dosing are necessary when using this treatment. We should also take note of some of the challenges associated with using low-dose IL-2 as a treatment for autoimmune diseases. For example, it can be difficult to determine the optimal dose and dosing schedule for each patient. In addition, there may be individual differences in how patients respond to low-dose IL-2 treatment. Overall, we believe that low-dose IL-2 shows promise as a treatment for autoimmune diseases, but more research is needed to fully understand its potential benefits and risks.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases* / immunology
  • Autoimmune Diseases* / therapy
  • Humans
  • Interleukin-2* / administration & dosage
  • Interleukin-2* / therapeutic use
  • Receptors, Interleukin-2 / immunology
  • Receptors, Interleukin-2 / metabolism
  • T-Lymphocytes, Regulatory* / immunology

Substances

  • Interleukin-2
  • Receptors, Interleukin-2