Abstract
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 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 factorα (rTNF-α) 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.
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Proebstle, T., Mitrovics, M., Schneider, M. et al. Recombinant interleukin-2 acts like a class I antiarrhythmic drug on human cardiac sodium channels. Pflügers Arch. 429, 462–469 (1995). https://doi.org/10.1007/BF00704150
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DOI: https://doi.org/10.1007/BF00704150