Methods: 10 patients with active and refractory SLE (SLEDAI ≥ 6; at least two different immunosuppressive therapies) were enroled into the trial and 2 patients were treated „off-label“ with the same regimen. The therapeutic regimen consisted of four treatment cycles each with daily subcutaneous injections of recombinant human IL-2 (aldesleukin) at single doses of 0.75, 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. Cells from peripheral blood were analysed by flow cytometry at every study visit before the IL-2 injections and one day after the 5th IL-2 injection. The primary objective was to show an increase in the percentage of CD25hi cells among CD3+CD4+Foxp3+CD127lo Treg cells by at least 100% (2-fold) after the 4th treatment cycle compared to baseline. Safety and tolerability were evaluated descriptively. Secondary objectives included the clinical responses assessed by SLEDAI and changes in serological and other immunological parameters.

Results: All 12 patients showed an effective and cycle-dependent increase in the percentage of CD25hi cells among Treg (p<0.001). 10 patients showed a reduction in SLEDAI (83.3%, p<0.05) and 8 patients achieved a clinical response (66.7%) with a complete disappearance of clinical manifestations such as rash, arthritis, myositis and alopecia. Levels of complement were significantly increased after the treatment compared to baseline (p<0.05). However, we could not observe a reduction in levels of anti-dsDNA-Abs. Treatment-related adverse events were generally mild and transient.

Conclusion: Low-dose IL-2 therapy is capable to safely and selectively expand the Treg population and to decrease disease activity in patients with active and refractory SLE. This study provides the basis for larger and placebo-controlled clincial studies aiming to prove the efficacy of this novel biologic treatment strategy.