What is the clinical evidence from this study?

Study design: Case-Control. Population: Atrial Fibrillation (n=367). Intervention: IL-11 vs. Healthy subjects. Primary outcome: Correlation between serum IL-11 and cardiac fibrosis marker BNP (r = 0.394, p=<0.001).

January 1, 2023

Interleukin-11 Is Elevated in Patients with Atrial Fibrillation, Correlates with Serum Fibrosis Markers, and Represents a Therapeutic Target for Atrial Fibrosis

Q: What are the key findings of this study?

Serum IL-11 levels were significantly correlated with cardiac fibrosis markers in AF patients (e.g., BNP r=0.394, p<0.001), and IL-11 inhibition attenuated atrial fibrosis in a mouse model.

Key Result

Serum IL-11 levels were significantly correlated with cardiac fibrosis markers in AF patients (e.g., BNP r=0.394, p<0.001), and IL-11 inhibition attenuated atrial fibrosis in a mouse model.

Study Design

Type

Case-Control (n=367)

Structured PICO

Is IL-11 elevated in AF patients and does IL-11 inhibition prevent atrial fibrosis in a mouse model?

Population

207 atrial fibrillation (AF) patients (76 persistent, 131 paroxysmal) and 160 healthy subjects; and Angiotensin II (Ang II)-treated fibrosis mouse models

Intervention

IL-11 antagonist (in mouse model)

Comparator

Healthy subjects (human cohort); untreated Ang II-infused mice (mouse model)

Outcome

Serum IL-11 levels and correlation with cardiac fibrosis markers (human); atrial fibrosis markers including Masson trichrome, α-SMA, and collagen I/III expression (mouse)surrogate

IL-11 is elevated in AF patients and correlates with fibrosis markers, while its inhibition attenuates atrial fibrosis in preclinical models, suggesting a potential therapeutic target.

Main Result

Effect estimate: r = 0.394

p-value: p=<0.001

Abstract

INTRODUCTION: Inflammatory cytokines are closely associated with developing cardiac fibrosis. This research aimed to explore the significant role of IL-11 in atrial fibrosis progression and potential therapeutic targets. METHODS: 207 AF patients and 160 healthy subjects were included in the case-control study. Blood samples were analyzed for the level of IL-11 by enzyme-linked immunosorbent assay (ELISA). Angiotensin II (Ang II)-treated fibrosis mouse models were generated, and expression of IL-11 mRNA and protein was detected by RT-qPCR and Western blot. IL-11 antagonist was used to evaluating atrial fibrosis-related markers. RESULTS: The persistent atrial fibrillation patients (n = 76) had significantly larger left atrial size, higher serum levels of hypertrophic protein BNP, proinflammatory cytokine high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) compared to paroxysmal atrial fibrillation patients (n = 131), and healthy subjects (all p < 0.05). Pearson correlation analysis revealed significant positive correlation between serum IL-11 and cardiac fibrosis markers BNP (r = 0.394, p < 0.001), CTX-I (r = 0.418, p < 0.001), PICP (r = 0.306, p < 0.001), PIIINP (r = 0.335, p < 0.001), and TGF-β1 (r = 0.273, p < 0.001). In the fibrosis mouse model, Ang II infusion significantly upregulated IL-11 mRNA and protein expression in the left atrium of mice (p < 0.05), as well as staining intensity of Masson trichrome, the intensity of α-SMA, and it increased mRNA expression of collagen I and III in atrial tissue. IL-11 antagonist treatment significantly attenuated Masson trichrome, number of α-SMA-positive myofibroblasts in atrial tissue. Also, it significantly reduced the p-ERK1/2 in atrial tissue of mice infused with Ang II (p < 0.05). CONCLUSIONS: IL-11 is upregulated in the serum of AF patients, and IL-11 inhibitor significantly inhibited Ang II-induced atrial fibrosis, a key pathological feature of AF. Therefore, IL-11 could be a potential therapeutic target for AF.

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