Key result
Treatment with a mouse anti-IL-5 neutralizing antibody aggravated doxorubicin-induced cardiac injury and dysfunction by promoting M1 macrophage differentiation and myocardial cell apoptosis.
Why the study?
Interleukins are associated with doxorubicin-induced cardiac injury, but whether interleukin-5 affects this injury and its underlying mechanisms remained unknown.
Does anti-IL-5-neutralizing antibody affect doxorubicin-induced cardiac injury and dysfunction in mice?
Does anti-IL-5-neutralizing antibody affect doxorubicin-induced cardiac injury and dysfunction in mice?
In a mouse model, anti-IL-5 neutralizing antibody aggravated doxorubicin-induced cardiac injury and dysfunction, suggesting a protective role for endogenous IL-5 against cardiotoxicity.
May caution anti-IL-5 use with doxorubicin; leaves open IL-5 cardioprotection in humans.
Previous studies have demonstrated that interleukins (ILs) are closely associated with doxorubicin (DOX)-induced cardiac injury. IL-5 is an important member of the IL family, and this study was performed to investigate whether IL-5 affects DOX-induced cardiac injury and its underlying mechanisms. The cardiac IL-5 expression was first detected and the results showed that cardiac IL-5 levels were significantly lower in DOX-treated mice, and IL-5 was mainly derived from cardiac macrophage (Mø). In addition, some DOX-treated mice received an injection of anti-IL-5-neutralizing antibody (nAb), and we found that treatment with a mouse anti-IL-5 nAb significantly upregulated the levels of myocardial injury markers, aggravated cardiac dysfunction, increased M1 macrophage (Mø1) and decreased M2 macrophage (Mø2) differentiation, and promoted apoptotic marker expression. Furthermore, the effect of mouse IL-5 nAb on DOX-induced Mø differentiation and its role on mouse cardiomyocyte (MCM) cells apoptosis were detected in vitro, and the results exhibited that mouse IL-5 nAb promoted Mø1 differentiation but inhibited Mø2 differentiation in vitro and alleviated apoptosis in MCM cells. Our results found a mouse anti-IL-5 nAb-aggravated DOX-induced cardiac injury and dysfunction by alleviating the inflammatory response and myocardial cell apoptosis.
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Xiao et al. (2020) studied Doxorubicin-induced cardiac injury. Anti-IL-5-neutralizing antibody vs. Doxorubicin alone was evaluated on Cardiac injury, cardiac dysfunction, macrophage differentiation, and apoptosis. Treatment with a mouse anti-IL-5 neutralizing antibody aggravated doxorubicin-induced cardiac injury and dysfunction by promoting M1 macrophage differentiation and myocardial cell apoptosis.
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