Low-dose interleukin-2 treatment increases the proportion of regulatory T cells in patients with rheumatic diseases: A meta-analysis

Abstract

Background: It is now accepted that immune tolerance disorders caused by inadequate Treg cell function or number are important factors in the development and progression of rheumatic diseases. There is increasing evidence that ld IL-2 treatment increases the proportion of Treg cells in patients' peripheral blood, but this conclusion is still controversial. Here, we performed a meta-analysis of reports documenting the proportion of Treg cells and the rate of adverse events in patients with rheumatic disease before and after the administration of ld IL-2 to better understand its effect and safety on Treg cells in the field of rheumatic diseases.

Methods: We systematically searched PubMed, Embase, Scopus, Cochrane Library, and Web of science databases up to 15th November 2022 and identified studies that reported the proportion of peripheral blood Treg cells before and after ld IL-2 treatment in patients with rheumatic disease. Random-effects model was used to perform a meta-analysis of Treg cell proportions before and after ld IL-2 administration, and a meta-regression analysis was performed to explore heterogeneity. Inconsistency was evaluated using the I-squared index (I²), and publication bias was assessed by examining funnel plot asymmetry using the Egger tests.

Results: Eighteen studies involving 1608 patients were included in the meta-analysis. The proportion of Treg cells in peripheral blood of these patients increased significantly after receiving ld IL-2 treatment [1.07 (95% CI 0.86,1.27), p < 0.001, I² = 67.3%]. Next, Meta-regression was performed for 5 variables including publish year, disease type, trail type and dosage and duration of the medication. The results suggest that these variables do not lead to high heterogeneity. (p = 0.698, 0.267, 0.502, 0.843, 0.560, respectively). And finally, statistical analysis showed no difference in adverse reactions between ld IL-2 group and control group in treatment [1.06 (95% CI 0.86,1.31), p = 0.586, I2 = 53.8%], which is unreliable because the data is so small.

Conclusions: Ld IL-2 does increase the proportion of peripheral blood Treg cells in patients with rheumatism, and single and cumulative doses must be considered when using ld IL-2. In addition, more studies on the safety of ld IL-2 are urgently needed.

Keywords: Low-dose interleukin-2 (ld IL-2); Meta-analysis; Regulatory T(Treg) cells; Rheumatic diseases.