New Investigator AwardAerobic exercise, but not flexibility/resistance exercise, reduces serum IL-18, CRP, and IL-6 independent of β-blockers, BMI, and psychosocial factors in older adults
Introduction
Elevated levels of inflammatory mediators have been associated with an increased risk and/or severity of chronic disease. Atherosclerosis and coronary artery disease are associated with greater levels of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α (Larsson et al., 2005, Ridker et al., 2003, Schwartz et al., 2003, Tzoulaki et al., 2005). Elevated blood pressure and congestive heart failure are associated with elevated serum CRP, IL-6, TNFα, and IL-1β (Barbieri et al., 2003, Blake et al., 2003, Torre-Amione, 2005, Vasan et al., 2003). Patients with metabolic disorders including Type II diabetes, metabolic syndrome, and obesity also have increased IL-6 and CRP (Das, 2001, Fernandez-Real and Ricart, 2003, Pradhan et al., 2001, Ridker et al., 2003). IL-18 is a pleiotropic inflammatory cytokine that is elevated in the serum of Type II diabetics and is a predictor of cardiovascular death and future coronary heart disease (Blankenberg et al., 2002, Blankenberg et al., 2003, Moriwaki et al., 2003). Aging is also considered to be an inflammatory state, and levels of inflammatory markers are predictors of mortality and disability (Kritchevsky et al., 2005).
Physical activity has been inversely associated with elevated inflammatory markers (Church et al., 2002) and this relationship has been demonstrated in older adults (Colbert et al., 2004, Geffken et al., 2001). Several studies in middle-aged adults reported that exercise and diet interventions resulting in weight loss reduced serum CRP, IL-6, and IL-18, whereas exercise training alone reduced serum CRP, IL-6, and blood mononuclear cell production of TNFα and IL-1α in patients at risk for heart disease (Esposito et al., 2003, Goldhammer et al., 2005, Smith et al., 1999, You et al., 2004). However, the findings from one exercise intervention study with older adult subjects showed no significant reduction in serum CRP (Hammett et al., 2004). Therefore, it is not clear whether an exercise intervention in older adults can significantly reduce CRP, IL-6, or IL-18. It is also not known what type of exercise may be most effective, as currently published trials have used primarily aerobic exercise. In addition, the mechanism(s) by which exercise may reduce inflammatory mediators have not been addressed, although changes in body fat or body mass index (BMI) have been suggested to play a role.
β-Adrenergic receptor activation may be one mechanism that mediates exercise-induced alteration of inflammatory mediators. β-Adrenergic receptor activation of adipocytes increases pro-inflammatory cytokine secretion, and β-adrenergic receptor density and activity may change with exercise training (Nieto et al., 1996). An association between β-blocker treatment and reduced CRP has also been reported (Jenkins et al., 2002). Another mechanism by which exercise may reduce inflammatory mediators involves alterations of psychosocial factors. Major depressive disorder, stress, and anxiety are associated with elevated inflammatory cytokines, and exercise has been shown to reduce clinical depression and anxiety (Black and Garbutt, 2002, Blumenthal et al., 1999, Dantzer et al., 1999, Kiecolt-Glaser and Glaser, 2002, King et al., 1993, Pitsavos et al., 2005, Suarez, 2004). Thus, more than one mechanism (psychosocial and physiological) may mediate the exercise-induced reduction of inflammatory factors.
There are two goals of this study: (1) determine the type(s) of exercise that may result in a reduction of serum inflammatory markers in older adults and (2) establish the extent to which β-adrenergic receptors and psychosocial factors mediate exercise-induced change in inflammatory markers. We hypothesize that aerobic exercise will be more effective than flexibility/resistance exercise in reducing serum inflammatory factors, and that both psychosocial factors and β-adrenergic receptor activation will mediate, in part, the reduction of inflammatory factors. Clearly, there are important clinical benefits to be obtained by understanding what type of exercise is most effective in reducing inflammation among older adults. In addition, an understanding of how exercise modulates inflammation could lead to the development of additional effective therapies.
Section snippets
Participant screening and randomization
Older adults were recruited from two different central Iowa communities through the placement of advertisements, by press releases in local newspapers, visits to senior citizen meal sites, churches and church groups, senior community service organizations, independent living housing facilities, and by friend referral. All procedures involving human subjects were approved by the Institutional Review Board for Human Subjects at Iowa State University and Des Moines University of Osteopathic
Health and fitness measures
Baseline characteristics of participants are shown in Table 1. Health/disease status was similar between groups, and there were no significant differences between the CARDIO and FLEX groups on the baseline health or fitness variables (see Table 1, Table 2). Use of statins was not different between groups, but there were a greater number of subjects in the cardio treated with daily aspirin therapy. When medications (statins and aspirin) were included as a covariate in subsequent analyses of
Discussion
To our knowledge, the findings from this study are the first to suggest that the type of exercise performed may impact the extent to which serum inflammatory mediators may be altered. Cardiovascular exercise reduced serum levels of IL-6, IL-18, and CRP whereas flexibility/moderate strength training did not have the same positive effect. We did, however, observe a reduction in TNFα in both groups, suggesting that flexibility/strength exercise may have some benefits. The change in plasma volume
Acknowledgments
This work was supported in part by a grant from NIAID, number R01 AI49956. David Senchina and Wanglok Lee also contributed to the experimental assays.
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