Interleukin 11 Therapy Causes Acute Left Ventricular Dysfunction
Author Information
Author(s): Mark Sweeney, Kate O’Fee, Chelsie Villanueva-Hayes, Ekhlas Rahman, Michael Lee, Chung Nga Tam, Eneko Pascual-Navarro, Henrike Maatz, Eric L Lindberg, Konstantinos Vanezis, Chrishan Ramachandra, Ivan Andrew, Emma R Jennings, Wei-Wen Lim, Anissa A Widjaja, David Carling, Derek J Hausenloy, Paul J R Barton
Primary Institution: Imperial College London
Hypothesis
Does interleukin 11 (IL11) cause direct cardiomyocyte toxicities that explain cardiac side effects associated with IL11 therapy?
Conclusion
Injection of IL11 directly activates IL11RA/JAK/STAT3 in cardiomyocytes to cause acute heart failure.
Supporting Evidence
- Injection of rmIL11 caused acute and dose-dependent impairment of left ventricular ejection fraction.
- Phosphorylation of STAT3 and JNK was increased following rmIL11 injection.
- Bulk RNA-seq revealed up-regulation of pro-inflammatory pathways after rmIL11 treatment.
- Cardiomyocyte-specific knockout models showed protection from rmIL11-induced cardiac impairment.
- Inhibition of JAK/STAT signaling prevented rmIL11-induced cardiac dysfunction.
Takeaway
Giving a substance called IL11 to mice made their hearts work poorly, showing that IL11 can be harmful to heart cells.
Methodology
Mice were injected with recombinant mouse IL11 and assessed for cardiac function using echocardiography and various molecular analyses.
Potential Biases
Potential conflicts of interest due to authors' involvement in patent applications related to IL11.
Limitations
The study primarily used mouse models, which may not fully replicate human responses to IL11 therapy.
Statistical Information
P-Value
<0.001
Statistical Significance
p<0.001
Digital Object Identifier (DOI)
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