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

R A Tio1, J Nieken, E G de Vries

  • 1Thoraxcenter, Department of Cardiology, University Hospital Groningen, P.O. Box 30.001, 9700, Groningen, The Netherlands. r.a.tio@thorax.azg.nl

European Journal of Heart Failure
|June 17, 2000
PubMed
Abstract

Insights

Recombinant interleukin-2 (rIL2) therapy in renal cell carcinoma patients reduced heart contractility and sympathetic activity. This negative inotropic effect may be linked to increased nitric oxide (NO) levels.

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.

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