Differential expression of cytokines in the rat heart in response to sustained volume overload

Objective: The present study aimed to investigate whether sustained volume overload is capable of inducing persistent upregulation of cardiac cytokines including tumor necrosis factor alpha (TNF)-alpha, interleukin (IL)-1beta, interleukin (IL)-6 and transforming growth factor (TGF)-beta(1). Methods and Results: Volume overload-induced heart hypertrophy in rats was established by aortacaval fistula, and the cardiac cytokines were measured in the myocardium from 1 to 4 weeks after operation. In the post-fistula rats, cardiac IL-1beta and IL-6 gene and protein levels were upregulated throughout the time of measurement. Immunohistochemistry demonstrated that IL-1beta and IL-6 immunoreactive cells were widely distributed in the myocardium in the earlier time intervals, and mainly localized in the regions close to the endocardium in the later time intervals. The cardiac IL-1beta immunoreactive cells were mainly localized in the blood vessels whereas the IL-6 positive cells were composed of non-myocytes and cardiomyocytes. TGF-beta(1) positive staining was increased in the myocardium up to 3 weeks after aortacaval fistula and then decreased to basal levels thereafter. In contrast to the activation of cardiac IL-1beta and IL-6 in response to volume overload, TNF-alpha expression appeared unaltered in response to sustained volume overload in the transcription and protein levels. Conclusion: The results of the present study indicate that sustained volume overload is capable of inducing persistent upregulation of some cardiac cytokines. In addition, the differential expressions of TNF-alpha, IL-1beta and IL-6 suggest that the induction of IL-6 and IL-1beta is independent of TNF-alpha mediated pathways in this animal model. (C) 2003 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.