Relationship between Inflammatory Cytokines and Indices of Cardiac Dysfunction following Intense Endurance Exercise

Abstract

Objectives Pro-inflammatory cytokines have been noted to increase following exercise but their relationship to exercise-induced cardiac dysfunction has not previously been investigated. We sought to evaluate whether exercise-induced cardiac dysfunction was associated with increases in cytokines, particularly the pro-inflammatory cytokines IL-1 beta, IL-12p70 and TNF alpha, which have been most implicated in cardiac pathology. Methods 40 well-trained endurance athletes underwent evaluation prior to and immediately following one of four endurance sporting events ranging from 3 to 11 hours duration. Cytokines (IL-1 beta, IL-6, IL-8, IL-10, IL-12p70 and TNF alpha) were analyzed by flow cytometry from serum samples collected within 50 minutes of race completion. Cardiac troponin (cTnI) and B-type natriuretic peptide were combined with an echocardiographic assessment of cardiac function, and a composite of cTnI > 0.04 mu g/L, BNP increase > 10 ng/L and a decrease in right ventricular ejection (RVEF) > 10% were prospectively defined as evidence of myocardial dysfunction. Results Relative to baseline, IL-6 IL-8 and IL-10 increased 8.5-, 2.9-, and 7.1-fold, respectively, P<0.0001. Thirty-one (78%), 19 (48%) and 18 (45%) of the athletes met the pre-specified criteria for significant cTnI, BNP and RVEF changes, respectively. TNF alpha, IL-12p70 were univariate predictors of Delta RVEF and Delta BNP whilst none of the anti-inflammatory cytokines were significantly associated with these measures. Ten athletes (25%, all athletes competing in the endurance event of longest duration) met criteria for exercise-induced myocardial dysfunction. In these 10 athletes with myocardial dysfunction, as compared to those without, there was significantly greater post-race expression of the pro-inflammatory cytokines IL-12p70 (8.1 +/- 3.8pg/ml vs. 2.5 +/- 2.6pg/ml, P<0.0001) and TNF alpha (6.5 +/- 3.1pg/ml vs. 2.0 +/- 2.5pg/ml, P<0.0001). Conclusion Cardiac dysfunction following intense endurance exercise was associated with increased expression of pro-inflammatory cytokines. This does not prove a causal relationship but provides rationale for further investigations into whether inflammation mediates exercise-induced myocardial dysfunction.