Low Dose Interleukin-2 in Patients With Stable Ischaemic Heart Disease and Acute Coronary Syndromes

Summary

The mainstay for treatment for acute coronary syndrome (ACS) focusses on re-establishing and maintaining the patency of vessels following coronary plaque disruption, through the use of anti-platelets and anticoagulants. Despite advances in management ACS still carries a high risk of morbidity and mortality, thus future management is likely to target other pathways. Recent studies indicate that CD4+ T cells, and more specifically Treg cells, are important for the control of post-ischemic immune responses and the promotion of myocardial healing. The investigators therefore hypothesise that expansion of Treg cells in patients with ACS dampens the activation of the immune response and promotes both plaque and myocardial healing. The investigators hypothesise that this can be achieved through subcutaneous administration of low doses of interleukin-2 (IL-2). IL-2 supplementation appears to be an attractive therapeutic option playing a key role in Treg cell development, expansion, survival and suppressive function.

Timeline

Start

2017-05-11

Primary completion

2019-02-21

Completion

2019-02-21

Publications

• Zhao TX, Sriranjan RS, Tuong ZK, Lu Y, Sage AP, Nus M, Hubsch A, Kaloyirou F, Vamvaka E, Helmy J, Kostapanos M, Jalaludeen N, Klatzmann D, Tedgui A, Rudd JHF, Horton SJ, Huntly BJP, Hoole SP, Bond SP, Clatworthy MR, Cheriyan J, Mallat Z. Regulatory T-Cell Response to Low-Dose Interleukin-2 in Ischemic Heart Disease. NEJM Evid. 2022 Jan;1(1):EVIDoa2100009. doi: 10.1056/EVIDoa2100009. Epub 2021 Nov 22.
• Liu L, Hu J, Lei H, Qin H, Wang C, Gui Y, Xu D. Regulatory T Cells in Pathological Cardiac Hypertrophy: Mechanisms and Therapeutic Potential. Cardiovasc Drugs Ther. 2024 Oct;38(5):999-1015. doi: 10.1007/s10557-023-07463-y. Epub 2023 May 15.
• Zhao TX, Kostapanos M, Griffiths C, Arbon EL, Hubsch A, Kaloyirou F, Helmy J, Hoole SP, Rudd JHF, Wood G, Burling K, Bond S, Cheriyan J, Mallat Z. Low-dose interleukin-2 in patients with stable ischaemic heart disease and acute coronary syndromes (LILACS): protocol and study rationale for a randomised, double-blind, placebo-controlled, phase I/II clinical trial. BMJ Open. 2018 Sep 17;8(9):e022452. doi: 10.1136/bmjopen-2018-022452.

Drugs

Indications