INTERLEUKIN-18 AS A THERAPEUTIC TARGET FOR WESTERN DIET-INDUCED CARDIOMYOPATHY.

Area of Science:

• Cardiovascular Research
• Metabolic Syndrome
• Immunology

Background:

• A Western diet (WD) high in saturated fats and sugars induces obesity and left ventricular dysfunction in mice.
• Pro-inflammatory cytokine Interleukin-18 (IL-18) is implicated in mediating this cardiac dysfunction.
• This study investigated the therapeutic potential of blocking IL-18.

Purpose of the Study:

• To determine if a blocking recombinant-murine IL-18 binding protein (IL-18BP) could rescue cardiac function in mice fed a WD.
• To assess the role of IL-18 in diet-induced cardiac dysfunction.

Main Methods:

• Adult C57BL/6J mice were fed a standard diet (SD) or a WD for 9 weeks.
• After 7 weeks, WD-fed mice received daily intraperitoneal injections of IL-18BP or a control for 2 weeks.
• Cardiac function was assessed using Doppler echocardiography, and IL-18 plasma levels were measured via ELISA.

Main Results:

• WD feeding significantly increased body weight, worsened glucose tolerance, and impaired diastolic function (increased isovolumetric relaxation time -IRT- and myocardial performance index -MPI-).
• IL-18BP treatment significantly improved IRT and MPI in WD-fed mice.
• IL-18BP did not significantly alter food intake, weight gain, or glucose tolerance.

Conclusions:

• IL-18BP effectively rescued cardiac function in mice experiencing WD-induced diastolic dysfunction.
• The beneficial effects of IL-18BP were independent of changes in body weight or glucose tolerance.
• These findings highlight the critical and independent role of IL-18 in diet-induced cardiac dysfunction.