Low-Dose IL-2 Rebalances Immunity in SLE, With Yuebo Jin, MD

Low-dose interleukin-2 (IL-2) therapy is showing growing promise as a novel approach to immune modulation in systemic lupus erythematosus (SLE), aiming not to suppress immunity but to restore balance.

New data supporting the feasibility and benefit of low-dose IL-2 from a multicenter, randomized, double-blind, phase 2b trial were presented at the American College of Rheumatology (ACR) Convergence 2025, held October 24–29 in Chicago, Illinois, by Yuebo Jin, MD, associate professor, Department of Rheumatology and Immunology, Peking University People’s Hospital, Beijing, China.

The trial evaluated 3 different doses of low-dose IL-2, 0.2, 0.5, and 1.0 million IU, in 152 patients with active SLE. Over 24 weeks, investigators found a clear dose-dependent benefit, with the highest dose achieving the strongest clinical responses: 60% of patients receiving 1.0 million IU reached SRI-4 response criteria compared with 23% of those on placebo.

Low-dose IL-2 was also associated with improvements across multiple organ systems, including skin, hematologic, and renal domains. Complement levels increased, and corticosteroid requirements decreased—an encouraging signal for patients struggling with long-term steroid dependence. Notably, infection rates were significantly lower in the IL-2 arms than in the placebo group, underscoring the distinct safety profile of immune-balancing rather than immune-suppressive therapy.

Mechanistically, the treatment selectively expanded regulatory T cells (Tregs) while reducing proinflammatory effector T cells, restoring the immune equilibrium that is often disrupted in lupus. In an interview with HCPLive onsite at the meeting, Jin noted that these effects make low-dose IL-2 a compelling candidate for combination strategies, potentially used alongside biologics or conventional immunosuppressants to maintain remission and minimize toxicity.

She also shared ongoing and future research that aims to deepen understanding of IL-2’s immunologic and metabolic effects, explore new long-acting and localized formulations, and develop AI-driven tools to predict treatment response using multiomics data.

"What's very interesting thing is that the infection rates in the IL-2 groups are significantly lower than placebo, which is very different from traditional immunosuppressants. In terms of immune response, low-dose IL-2 expanded Treg cells and help rebalance Treg and effector T-cells [and] is working the way we expected," Jin said.

Jin had no disclosures to report.

Reference

Zhang X, Feng R, Li Z, He J. Low-dose Interleukin-2 Therapy in Systemic Lupus Erythematosus: a double-blind, randomised, placebo-controlled, phase IIb trial. Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #LB01