Key result
Low-dose IL-2 prevents cardiac dysfunction in rheumatic heart disease rats by increasing regulatory T cells.
Why the study?
Compliance with monthly penicillin to prevent acute rheumatic fever progression is poor, no specific therapy treats the autoimmune process, and better tools are needed to slow disease progression.
Does low-dose interleukin-2 therapy prevent cardiac functional and histological changes in a rat model of rheumatic heart disease?
Does low-dose interleukin-2 therapy prevent cardiac functional and histological changes in a rat model of rheumatic heart disease?
Low-dose interleukin-2 therapy prevents cardiac inflammation and reduces cross-reactive antibodies in a rat model of rheumatic heart disease, suggesting potential as a novel immunotherapeutic agent.
Hypothesis-generating for low-dose IL-2 in rheumatic heart disease; should not yet change clinical practice.
Acute rheumatic fever (ARF) is an autoimmune disease triggered by antibodies and T cells targeting the group A Streptococcus (GAS, Strep A) bacterium, often leading to rheumatic heart disease (RHD) and Sydenham’s chorea. Long-term monthly penicillin injections are recognized as a cornerstone of public health programs to prevent Strep A reinfection and progression of ARF. However, compliance is poor, and better tools are required to slow disease progression. Preclinical evidence suggests that this can be achieved. Using a rat model that replicates post-streptococcal autoimmune complications, we explored the potential of low-dose interleukin-2 (LD-IL-2) as an immunotherapeutic intervention for ARF/RHD. In this model, injections of recombinant M protein from Strep A type 5 (rM5) to Lewis rats induce cardiac tissue inflammation, conduction abnormalities, and cross-reactive antibodies against cardiac and brain proteins central to disease pathogenesis. In animals injected with rM5 and treated with LD-IL-2, no cardiac functional or histological changes was observed. LD-IL-2 therapy effectively reduced the production of cross-reactive antibodies raised against host proteins and significantly increased regulatory T cells in the mediastinal lymph nodes. These novel findings suggest that LD-IL-2 will be an effective immunotherapeutic agent for treating ARF and has the potential to replace the standard monthly penicillin injections. IMPORTANCE Post-streptococcal autoimmune syndromes, including acute rheumatic fever, rheumatic heart disease, and Sydenham’s chorea, represent a significant yet often under-recognized health and economic burden. This is especially true in low-income countries and among Indigenous populations in high-income nations, where the disease burden is most severe. These conditions arise from an autoimmune response to group A Streptococcus infections, leading to long-term health complications, disability, and premature death. Despite their widespread impact, no vaccine is currently available to prevent reinfections, and no specific therapy exists to treat the resulting autoimmune process. This study uses a rat model of rheumatic heart disease to evaluate the potential of low-dose interleukin 2 therapy in improving clinical outcomes and reducing the incidence of autoimmune diseases triggered by streptococcal infections.
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Rafeek et al. (2025) studied Acute rheumatic fever and rheumatic heart disease. Low-dose interleukin-2 (LD-IL-2) vs. No LD-IL-2 treatment was evaluated on Cardiac functional or histological changes, cross-reactive antibodies, and regulatory T cells. In a rat model of rheumatic heart disease, low-dose interleukin-2 therapy prevented cardiac functional and histological changes, reduced cross-reactive antibodies, and increased regulatory T cells.