Negative inotropic effects of recombinant interleukin 2 in patients without left ventricular dysfunction

Area of Science:

• Cardiology
• Oncology
• Immunology

Background:

• Recombinant interleukin-2 (rIL2) has demonstrated negative inotropic properties in experimental models.
• These effects have not been previously studied in humans with normal left ventricular function.

Purpose of the Study:

• To investigate the effects of low-dose subcutaneous rIL2 on cardiac function and autonomic activity in renal cell carcinoma patients.
• To explore the potential role of nitric oxide (NO) and inflammatory cytokines in mediating these effects.

Main Methods:

• Seventeen renal cell carcinoma patients receiving rIL2 therapy were assessed before and after treatment.
• Measurements included left ventricular ejection fraction (echocardiography), heart rate variability (24-h ECG), and plasma levels of TNF-alpha, IL-1beta, and NOx.
• rIL2 was administered subcutaneously at a low dose.

Main Results:

• Left ventricular ejection fraction decreased significantly (54±7% to 50±6%, P=0.012).
• Heart rate increased (87±13 to 94±13 bpm, P=0.031), and all heart rate variability parameters decreased, indicating reduced sympathetic activity.
• Plasma nitrate (NOx) levels increased significantly (22.8±14.4 to 41.8±26.6 µmol/l, P=0.007).
• No significant changes were observed in TNF-alpha or IL-1beta levels.

Conclusions:

• Low-dose rIL2 exhibits a negative inotropic effect in humans, potentially mediated by increased nitric oxide concentrations.
• rIL2 therapy also appears to reduce sympathetic nervous system activity, as indicated by heart rate variability changes.