Age-Dependent Atrial Remodeling Induced by Recombinant Human Interleukin-11: Implications for Atrial Flutter/Fibrillation

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Abstract
Recombinant human interleukin-11 (rhIL-11) has been used to alleviate side effects caused by chemotherapy in patients with neoplastic diseases and as an experimental anti-inflammatory agent. Its use in elderly patients has been associated with increased frequency of atrial flutter/fibrillation (AF). The mechanism of the latter phenomenon was studied in a rat model in vivo. Adult and old Fischer 344 rats fed with either normal diet or sodium-restricted diets were treated with rhIL-11 or vehicle (control) (1 mg/kg/day, i.p., 7 days); cardiac electrophysiologic parameters and atrial dimensions were determined. In adult rats, rhIL-11 was without effect, and atrial pacing did not induce AF. In contrast, in old rats, rhIL-11 shortened atrial refractoriness and increased atrial dimensions. Also, atrial pacing induced AF in old rats treated with rhIL-11 more than in controls. These effects of rhIL-11 in old rats were reversed by sodium-restricted diet. It was concluded that rhIL-11 induces age-dependent atrial remodeling manifested by atrial stretch and reduced atrial refractoriness, which favor AF. Na retention is the most likely mechanism underlying this effect of rhIL-11.