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

Experimental data have shown that rIL2 has negative inotropic properties. T his has not been investigated in humans with normal left ventricular functi on. Seventeen consecutive renal cell carcinoma patients who received rIL2 t herapy because of dissemination were analyzed before and after treatment wi th a low dose of rIL2 subcutaneously. Left ventricular ejection fraction (e chocardiography), heart rate variability parameters (24 h electrocardiograp hy), and TNF alpha, IL1 beta and nitric oxide metabolites (NOx) were measur ed. LVEF decreased from 54 +/- 7 to 50 +/- 6% (mean +/- S.D.; P = 0.012), w ith a concomitant increase in heart rate from 87 +/- 13 to 94 +/- 13 beats/ min (P = 0.031). All frequency domain HRV parameters decreased: the total p ower from 18.0 +/- 7.9 to 14.0 +/- 5.0 ms (P = 0.001), the low frequency fr om 10.3 +/- 5.4 to 8.3 +/- 3.4 ms (P = 0.001), and the high frequency from 6.3 +/- 2.6 to 4.5 +/- 1.1 ms (P = 0.001), There was no measurable effect o n TNF alpha, IL1 beta concentrations. Plasma levels of nitrate (NOx) increa sed from 22.8 +/- 14.4 to 41.8 +/- 26.6 mu mol/l (P = 0.007). Conclusions: A low dose of rIL2 has a negative inotropic effect that may be mediated by increased NO concentrations. It also reduces sympathetic activity as reflec ted in HRV parameters. (C) 2000 European Society of Cardiology. All rights reserved.