Low dose of IL-2 combined with rapamycin restores and maintains the long-term balance of Th17/Treg cells in refractory SLE patients

Abstract

Background The development of Systemic lupus erythematosus (SLE) has been associated with the balance of Th17 and Treg cells. IL-2 and rapamycin can influence the populations of both Th17 and Treg cells. However, it is unclear whether low dose of IL-2 and rapamycin can relieve the symptoms of SLE patients and what is the mechanisms. In this study, we aim to analyze the effect of low dose of IL-2 plus rapamycin on the number of Tregs, Th17 cells and the ratio of Th17/Treg cells, as well as to evaluate its therapeutic efficacy in refractory SLE patients. Result Fifty refractory SLE patients and 70 healthy controls were enrolled and followed up for 24 weeks. We found that compared with HC, the refractory SLE patients had a lower number of Tregs, a similar number of Th17 cells, but an increased ratio of Th17/Treg. After the treatment, the number of Tregs of the patients at 12th and 24th week was significantly increased. While the number of Th17 cells was unchanged, the ratio of Th17/Treg was significantly decreased at both 6 weeks and 24 weeks. After 6, 12 and 24 weeks of treatment, the SLEDAI score was significantly reduced. The prednison dosage at 6th,12th and 24th week post treatment was significantly decreased. Conclusion Our results support that the reduction of Tregs and the imbalance of Th17/Treg cells were correlated with the occurrence and development of refractory SLE. Low dose of IL-2 combined with rapamycin was able to restore the number of Tregs and the balance of Th17/Treg cells. As a result, this approach was able to induce immune tolerance and promote disease remission, allowing for the reduction in prednisone dosage. Trial registration ChiCTR-IPR-16009451 Registration date: 2016/10/16

Low-Dose IL-2 Therapy in Autoimmune and Rheumatic Diseases

“…In addition, a single-center, uncontrolled study investigated clinical and immunological responses of a combination therapy with low-dose IL-2 applied monthly for 3-5 days and continuous treatment with rapamycin every other day in 50 patients with refractory SLE. The combination therapy was applied for 24 weeks and significantly reduced disease activity and prednisolone dose compared to baseline for up to 24 weeks ( 60 ).…”

Relevance of Essential Trace Elements in Nutrition and Drinking Water for Human Health and Autoimmune Disease Risk

“…In a number of autoimmune diseases, an altered Th17/Treg ratio has been shown [22], particularly a drastic drop in the T-reg population. In many cases, the successful treatment of a number of systemic autoimmune diseases by using different molecules and treatment approaches may also be linked to the restoration of the Th17/Treg imbalance and/or of cellular functional properties that had been shown for example in MS and SLE [23][24][25][26].…”

Th Cytokine Profile in Childhood-Onset Systemic Lupus Erythematosus

“…In addition, low-dose IL-2 treatment in adult SLE patients increased Tregs in the blood and reduced the number of Th17 cells, thus exerting an immunosuppressive effect. At the same time, the SLEDAI-2K score after 12 weeks of treatment was found to be signi cantly reduced compared with that before treatment, and hormone levels were reduced, signi cantly alleviating disease [21]. It was also found in mouse studies that IL-2 can regulate the Th17 cell/Treg balance, enhance the function of Tregs, and inhibit Th17 cell differentiation [22].…”