Recombinant interleukin-2 acts like a class I antiarrhythmic drug on human cardiac sodium channels.
Human recombinant interleukin-2 (rIL-2) was bath-applied to isolated human cardiocytes while sodium currents were triggered and registered using the whole-cell recording technique. In the presence of the cytokine the sodium currents were reversibly blocked, 50% peak current reduction occurring at a concentration of 500 U/ml. The current-voltage relationship was not affected, but the steady-state inactivation curve was not affected, but the steady-state inactivation curve was shifted in the negative direction by 15 mV. When 35% of the sodium current was blocked the time constant of recovery from block at -135 mV was in the range of 63 +/- 27 ms. Use dependence was observed only at stimulation frequencies above 4 Hz. Addition of a polyclonal anti-IL-2 antibody to the extracellular solution prevented all of the above effects, while incubation of the cells with a function-blocking monoclonal anti-IL-2 receptor antibody had no influence on the described rIL-2 action. In contrast to rIL-2, recombinant tumor necrosis factor alpha (rTNF-alpha) did not affect the sodium currents. It is concluded that rIL-2 acts like a class I antiarrhythmic drug on human cardiac sodium channels. This might explain some of its proarrhythmic side effects when given intravenously in high doses.
Proebstle
T
T
Abteilung für Allgemeine Physiologie der Universität Ulm, Germany.
Mitrovics
M
M
Schneider
M
M
Hombach
V
V
Rüdel
R
R
D000906:Antibodies; D016207:Cytokines / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D011995:Recombination, Genetic; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000187:drug effects*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000906:Antibodies; D016207:Cytokines; D007376:Interleukin-2; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D014409:Tumor Necrosis Factor-alpha