Background/Purpose

Interleukin-2 (IL-2) is crucial for the growth and survival of regulatory T cells (Treg), and thus for the control of autoimmunity. In previous studies we have proven a causal relationship between an acquired IL-2-deficiency, defects in Treg biology and the development of systemic lupus erythematosus (SLE). Accordingly, we showed that compensation of IL-2 deficiency by IL-2 therapy corrects associated Treg defects and ameliorates already established disease in lupus-prone mice, providing the rationales for an IL-2-based immunotherapy of SLE in order to restore Treg activity an thus to re-establish endogenous mechanisms of tolerance that can counteract autoimmunity.

Here we report a rapid and robust reduction of disease activity in parallel to a remarkable expansion of the Treg population by an off-label therapy with low-dose IL-2 in two patients with a long-term history of SLE and increased disease activity refractory or intolerant to a large variety of approved and experimental therapies.

Methods

The therapeutic regimen consisted of four treatment cycles each with daily subcutaneous injections of recombinant human IL-2 (aldesleukin; Proleukin®) at single doses of 1.5 or 3.0 million IU on five consecutive days separated by washout-periods of 9-16 days and followed by a 9-week follow-up period. Disease activity was determined by the SLEDAI at defined time points during the study. Cells from peripheral blood were analyzed by flow cytometry at the indicated time points. Written informed consent was obtained from the patient prior to the initiation of the off-label treatment with IL-2.

Results

In the first treated patient, disease activity rapidly decreased already after one treatment cycle, while in the second patient a reduction in disease activity was observed two weeks later. During the following treatment cycles disease activity further decreased or remained low due to disappearance of clinical manifestations such as arthritis, myositis and skin rash. In addition and unexpectedly levels of anti-dsDNA-antibodies considerably declined in both patients. The clinical response was associated with cyclic and treatment-related increases of the CD25hiFoxp3+CD127lo Treg population in the peripheral blood. The therapy was very well tolerated and adverse events were generally mild and transient.

Conclusion

These data provide the first evidence for the clinical efficacy of low-dose IL-2-therapy in conjunction with the boosting of Treg activity in SLE and strongly support the rationales of this selective biological treatment strategy.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/induction-of-clinical-remission-by-low-dose-interleukin-2-in-refractory-sle/