Key result
IL-13 and IFN-γ preserve fractional shortening and reduce myocardial fibrosis via macrophage polarization in mice.
Why the study?
Although cancer is commonly associated with adverse cardiovascular outcomes, emerging evidence suggests tumor-derived systemic signals may unexpectedly modulate cardiac remodeling. This study tested whether tumor progression improves cardiac function under pressure overload through secretion of interleukin-13 and interferon-γ.
Does tumor progression or intravenous administration of IL-13 and IFN-γ improve cardiac function and reduce fibrotic remodeling in mice with pressure overload induced by transverse aortic constriction?
Does tumor progression or intravenous administration of IL-13 and IFN-γ improve cardiac function and reduce fibrotic remodeling in mice with pressure overload induced by transverse aortic constriction?
Tumor-derived cytokines IL-13 and IFN-γ ameliorate pressure overload-induced cardiac dysfunction and fibrosis in mice by shifting cardiac macrophages toward a reparative phenotype, suggesting a potential cytokine-dependent therapeutic strategy for heart failure.
Answers are grounded in this paper and cite their sources.
May warrant preclinical cytokine studies in HF models; leaves open translation to human pressure-overload cardiomyopathy.
Cardiac dysfunction induced by chronic pressure overload is characterized by progressive contractile impairment and fibrotic remodeling. Although cancer is commonly associated with adverse cardiovascular outcomes, emerging evidence suggests that tumor-derived systemic signals may modulate cardiac remodeling in unexpected ways. We tested the hypothesis that tumor progression improves cardiac function under pressure overload through secretion of the cytokines interleukin-13 (IL-13) and interferon-γ (IFN-γ). To do so, Pressure overload was induced in mice by transverse aortic constriction (TAC). Syngeneic tumors were established by subcutaneous implantation of cancer cells. Cardiac function was assessed by serial echocardiography, and myocardial remodeling was evaluated by histological fibrosis staining and molecular analysis. Circulating cytokines were profiled in tumor-bearing mice. Recombinant IL-13 and IFN-γ were intravenously administered to TAC mice in the absence of tumors to assess their direct effects on cardiac function and remodeling. Tumor-bearing TAC mice displayed significantly preserved cardiac function compared with non-tumor-bearing TAC controls, as reflected by improved fractional shortening. Consistently, Myocardial fibrosis was significantly reduced in tumor-bearing mice. Systemic cytokine profiling identified IL-13 and IFN-γ as prominently elevated tumor-derived factors. Intravenous administration of IL-13 and IFN-γ to TAC operated mice was sufficient to mimic the tumor-associated improvement in cardiac function and attenuation of fibrotic remodeling. To further understand the mechanism that is responsible for mediating this phenotype, immune profiling of cardiac tissue was performed and it has revealed a marked immune-modulation in the heart, especially a shift in macrophage polarization toward a reparative phenotype, characterized by reduced pro-fibrotic inflammatory markers and increased expression of genes associated with tissue repair. In conclusion, tumor-derived IL-13 and IFN-γ ameliorate pressure overload-induced cardiac dysfunction by reshaping the cardiac immune landscape, particularly through macrophage polarization toward a reparative phenotype. These findings identify immune-modulation as a key mechanism underlying tumor-heart crosstalk and highlight IL-13 and IFN-γ as potential therapeutic mediators of adverse cardiac remodeling in heart failure. These results highlight cytokine-dependent treatment as a new therapeutic strategy for cardiovascular diseases.
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L Awwad (2026) studied Pressure overload-induced cardiac dysfunction. Syngeneic tumor implantation or intravenous recombinant IL-13 and IFN-γ vs. Non-tumor-bearing or untreated TAC control mice was evaluated on Cardiac function (fractional shortening) and myocardial fibrosis. Intravenous IL-13 and IFN-γ or tumor implantation preserved fractional shortening and reduced myocardial fibrosis in TAC mice via reparative macrophage polarization.
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