Efficacy, safety and the lymphocyte subsets changes of low-dose IL-2 in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

ABSTRACT

INTRODUCTION: Existing therapies of systemic lupus erythematosus (SLE) are efficacious only in certain patients. Developing new treatment methods is urgent. This meta-analysis aimed to evaluate the efficacy and safety of low-dose IL-2 (LD-IL-2). METHODS: According to published data from PubMed, Web of Science, Embase, ClinicalTrials.gov, MEDLINE, MEDLINE, Web of Knowledge, Cochrane Library, and FDA.gov, eight trials were included. RESULTS: After the LD-IL-2 treatment, 54.8% of patients had distinct clinical remission. The SRI-4 response rates were 0.819 (95% confidence interval [CI] 0.745-0.894), and the SELENA-SLEDAI scores were significantly decreased (SMD = -2.109, 95% CI [-3.271, -0.947], p < .001). Besides, the proportions of CD4+ T (SMD = 0.614, 95% CI [0.250, 0.979], p = .001) and Treg cells (SMD = 1.096, 95% CI [0.544, 1.649], p < .001) were increased dramatically after LD-IL-2 treatment, while there were no statistical differences in the proportions of CD8+ T cells, Th1 cells, Th2 cells, and Th17 cells (p > .05). Besides, the proportions of Th17 (SMD = 1.121, 95% CI [0.709, 1.533], p < .001) and Treg (SMD = 0.655, 95% CI [0.273, 1.038], p = .001) were significantly increased after receiving subcutaneously 0.5 million IU of LD-IL-2 treatment per day for 5 days, but there were no statistical differences in the proportions of Treg after receiving 1 million IU every other day subcutaneously of LD-IL-2 treatment. Injection site reaction and fever were common side effects of IL-2, which occurred in 33.1% and 14.4% of patients. No serious adverse events were reported. CONCLUSION: LD-IL-2 was promising and well-tolerated in treating SLE, which could promote Treg's proliferation and functional recovery. Injecting 0.5 million IU of IL-2 daily can better induce the differentiation of Treg cells and maintain immune homeostasis than injecting 1 million IU every other day.