Negative inotropic effects of recombinant interleukin 2 in patients without left ventricular dysfunction.
Experimental data have shown that rIL2 has negative inotropic properties. This has not been investigated in humans with normal left ventricular function. Seventeen consecutive renal cell carcinoma patients who received rIL2 therapy because of dissemination were analyzed before and after treatment with a low dose of rIL2 subcutaneously. Left ventricular ejection fraction (echocardiography), heart rate variability parameters (24 h electrocardiography), and TNF alpha, IL1 beta and nitric oxide metabolites (NO(x)) were measured. LVEF decreased from 54+/-7 to 50+/-6% (mean+/-S.D.; P=0.012), with 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 power from 18.0+/-7.9 to 14.0+/-5.0 ms (P=0.001), the low frequency from 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 on TNF alpha, IL1 beta concentrations. Plasma levels of nitrate (NO(x)) increased from 22.8+/-14.4 to 41.8+/-26.6 micromol/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 reflected in HRV parameters.
Tio
R A
RA
Thoraxcenter, Department of Cardiology, University Hospital Groningen, P.O. Box 30.001, 9700, Groningen, The Netherlands. r.a.tio@thorax.azg.nl
Nieken
J
J
de Vries
E G
EG
Pfeiffer
C
C
de Jongste
M J
MJ
Pieper
E
E
Moshage
H
H
Limburg
P C
PC
Mulder
N H
NH
D000328:Adult; D000368:Aged; D001341:Autonomic Nervous System / Q000503:physiopathology; D002292:Carcinoma, Renal Cell / Q000503:physiopathology; D004562:Electrocardiography; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007680:Kidney Neoplasms / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000494:pharmacology; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
D007376:Interleukin-2; D011994:Recombinant Proteins