Are elevations of N-terminal probrain natriuretic peptide in endurance athletes after prolonged strenuous exercise due to systemic inflammatory cytokines?

Letter to the Editor Are elevations of N-terminal probrain natriuretic peptide in endurance athletes after prolonged strenuous exercise due to systemic inflammatory cytokines? To the Editor: We read with interest the paper by Scharhag et al1 whereby they examined an increase in plasma brain natriuretic peptide (BNP) (N-terminal BNP) after strenuous exercise in endurance athletes. We note also that the authors concluded that the increase in N-terminal proBNP is unlikely to reflect underlying cardiovascular disease or direct myocardial damage as a result of the strenuous exercise. Rather, the BNP is likely to reflect a cytoprotective mechanism. We believe, based on the literature, that indeed BNP would be cytoprotective; however, the mechanism for its release was not found in the study by Scharhag et al.1 We would like to suggest that one likely mechanism may be systemic inflammation as a result of strenuous exercise. Strenuous exercise may also be akin to infectious disease states that likewise promote a release of BNP into the plasma. Specific changes have been observed—both after strenuous exercise and in infectious disease states—that include the acute phase response, leukocyte mobilization and activation, release of inflammatory mediators (cytokines), tissue damage and cell infiltration, the production of free radicals and activation of the complement, coagulation and fibrinolytic pathways.2 Furthermore, Brenner et al2 showed that prolonged exercise induces a significant increase in IL-6 and tumor necrosis factor a plasma levels, the mobilization of cytotoxic cell populations, and increased natural killer cell cytotoxic activity, all suggesting that prolonged exercise was effective in activating several components of the inflammatory response.

Certainly, inflammation and cytokine release may be responsible for BNP spillover into the circulation.3 For example, an increase in circulating BNP, but not atrial natriuretic peptide, is observed coincident with cardiac allograft rejection that is reversed upon treatment with antilymphocyte therapy, suggesting that proinflammatory cytokines may uniquely modulate BNP gene expression and secretion.4 Therefore, in the future, it may be a worthwhile hypothesis to test that exerciseinduced cytokines promote the release of BNP following strenuous exercise. Am Heart J 2006;152:e1. 0002-8703/$ - see front matter DOI of original article:10.1016/j.ahj.2005.01.051 doi:10.1016/j.ahj.2006.03.022

Craig McLachlan, PhD, MPH E-mail: [email protected] Peter Mossop, MBBS, FRACR Center for Molecular Medicine ASTAR, Singapore

References 1. Scharhag J, Herrmann M, Urhausen A, et al. Independent elevations of N-terminal pro-brain natriuretic peptide and cardiac troponins in endurance athletes after prolonged strenuous exercise. Am Heart J 2005;150:1128 - 34. 2. Brenner IK, Natale VM, Vasiliou P, et al. Impact of three different types of exercise on components of the inflammatory response. Eur J Appl Physiol Occup Physiol 1999;80:452 - 60. 3. McLachlan CS, Mossop P. Levosimendan and plasma BNP levels: do inflammatory cytokines regulate BNP in chronic decompensated heart failure? Eur J Heart Fail 2006;8:216 - 7. 4. Ma KK, Ogawa T, de Bold AJ. Selective upregulation of cardiac brain natriuretic peptide at the transcriptional and translational levels by pro-inflammatory cytokines and by conditioned medium derived from mixed lymphocyte reactions via p38 MAP kinase. J Mol Cell Cardiol 2004;36:505 - 13.