Low-dose interleukin-2 therapy: a promising targeted therapeutic approach for systemic lupus erythematosus

TY - JOUR

T1 - Low-dose interleukin-2 therapy: a promising targeted therapeutic approach for systemic lupus erythematosus

AU - Akbarzadeh, Reza

AU - Riemekasten, Gabriela

AU - Humrich, Jens Y

N1 - Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

PY - 2023/3/1

Y1 - 2023/3/1

N2 - PURPOSE OF REVIEW: Low-dose interleukin-2 (IL-2) therapy is increasingly recognized as a promising novel therapeutic concept in inflammatory and autoimmune diseases, in particular in systemic lupus erythematosus (SLE). As IL-2 is indispensable for the growth and survival of regulatory T cells (Treg), deficiency of this regulatory cytokine plays a significant role in immune dysregulation and breach of tolerance in SLE. Recovery of Treg activity by low-dose IL-2 therapy directly interferes with the immune pathology in SLE and thus can be considered a targeted treatment approach with a unique and physiological mode of action.RECENT FINDINGS: In this review, the pathophysiological rationales behind the concept of low-dose IL-2 therapy in SLE will be explained and major advances in translational research and the clinical development of low-dose IL-2 therapy focusing on the results from two recent, randomized and placebo-controlled phase 2 trials will be highlighted.SUMMARY: Several clinical studies including two recent randomized trials have proven the very good safety profile of low-dose IL-2 therapy and its capability to selectively recover and expand the Treg population in patients with active SLE. Given the emerging evidence for the clinical potential of low-dose IL-2 therapy in SLE, these studies strongly confirm the pathophysiological concept behind this targeted therapeutic approach in SLE and provide a robust basis for establishing further in-depth and confirmatory clinical trials testing the application of low-dose IL-2 in SLE and other autoimmune diseases.

AB - PURPOSE OF REVIEW: Low-dose interleukin-2 (IL-2) therapy is increasingly recognized as a promising novel therapeutic concept in inflammatory and autoimmune diseases, in particular in systemic lupus erythematosus (SLE). As IL-2 is indispensable for the growth and survival of regulatory T cells (Treg), deficiency of this regulatory cytokine plays a significant role in immune dysregulation and breach of tolerance in SLE. Recovery of Treg activity by low-dose IL-2 therapy directly interferes with the immune pathology in SLE and thus can be considered a targeted treatment approach with a unique and physiological mode of action.RECENT FINDINGS: In this review, the pathophysiological rationales behind the concept of low-dose IL-2 therapy in SLE will be explained and major advances in translational research and the clinical development of low-dose IL-2 therapy focusing on the results from two recent, randomized and placebo-controlled phase 2 trials will be highlighted.SUMMARY: Several clinical studies including two recent randomized trials have proven the very good safety profile of low-dose IL-2 therapy and its capability to selectively recover and expand the Treg population in patients with active SLE. Given the emerging evidence for the clinical potential of low-dose IL-2 therapy in SLE, these studies strongly confirm the pathophysiological concept behind this targeted therapeutic approach in SLE and provide a robust basis for establishing further in-depth and confirmatory clinical trials testing the application of low-dose IL-2 in SLE and other autoimmune diseases.

KW - Cytokines

KW - Humans

KW - Immunotherapy/methods

KW - Interleukin-2/therapeutic use

KW - Lupus Erythematosus, Systemic

KW - T-Lymphocytes, Regulatory

U2 - 10.1097/BOR.0000000000000924

DO - 10.1097/BOR.0000000000000924

M3 - SCORING: Review article

C2 - 36563007

VL - 35

SP - 98

EP - 106

JO - CURR OPIN RHEUMATOL

JF - CURR OPIN RHEUMATOL

SN - 1040-8711

IS - 2

ER -