Electrophysiologic effects of rhIL-11 on single human atrial myocytes.

Administration of recombinant human interleukin-11 (rhIL-11) for cancer treatment has been reported to be associated with an increase incidence of atrial fibrillation in elderly patients. To elucidate the mechanism of this action, we investigated the direct electrophysiologic effect of rhIL-11 on action potential (AP) and currents recorded from single human atrial myocytes (HuAM). HuAM were isolated from samples of atrial appendages of patients undergoing corrective cardiac surgery. Patch-clamped HuAM were superfused with a Tyrode solution appropriately modified to measure AP, calcium current (ICa,L), transient outward current (Ito) and the pacemaker current If. At therapeutic concentrations (10-100 ng/ml), rhIL-11 did not modify the AP profile either in whole-cell or perforated-patch configuration. ICa,L evoked by a step to 0 mV from a holding potential (HP) of -70 mV was 370±45 pA in control (n=5) and 379±48 pA (n=3) and 368±42 pA (n=5) in the presence of 10 and 50 ng/ml rhIL-11, respectively. The amplitude and activation of Ito were not modified by rhIL-11 (at 60 mV: 2.1±0.2 nA in control n=10, vs. 1.9±0.2 nA n=7 and 2.1±0.2 nA n=5, in HuAM bathed with 10 and 50 ng/ml rhIL-11, respectively, n.s.). If was evoked by hyperpolarization to -60 / -140 mV from HP of -40 mV; Boltzmann fitting of the activation curve was used to determine the midpoint (VH) and the maximal amplitude (Imax). If activation was not modified by rhIL-11: Imax was 173±34 pA in control (n=10) and 159±35 pA and 117±14 pA in the presence of 10 and 50 ng/ml rhIL-11, respectively (n=5 for both, n.s.); VH was -99±3 mV in control and -98±4 mV and -94±2 mV in the presence of 10 and 50 ng/ml rhIL-11, respectively (n.s.). Thus, it is unlikely that direct alterations of membrane potential and currents of HuAM are the basis for the arrhythmogenic effect of rhIL-11.