Long-term exercise and atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease

Context Increasing evidence demonstrates that atherosclerosis is an immunol ogically mediated disease in which the secretion of atherogenic and atherop rotective cytokines, by infiltrating blood mononuclear cells, plays an impo rtant role. It is not known whether long-term exercise alters this atheroge nic and atheroprotedive activity directly. Objective To determine the effect of long-term exercise on the atherogenic activity of blood mononuclear cells in persons at risk of developing ischem ic heart disease. Design Before-after trial using a 6-month individualized, supervised exerci se program, with an enrollment period from December 1996 to October 1997. Setting Hospital-based community wellness center. Participants Of 110 persons who responded to a public request for volunteer s, 52 met the inclusion criteria (risk ratio for myocardial infarction grea ter than or equal to 1.7 based on serum complement and/or C-reactive protei n levels, and normal exercise treadmill test results). Forty-three of the 5 2 enrollees (25 women [mean age, 49.7 years] and 18 men [mean age, 48.1 yea rs]) completed the study; 9 withdrew for personal reasons. Additional risk factors for ischemic heart disease included hypercholesterolemia (65.1%), a family history of coronary heart disease (62.8%), inactivity (60.5%), hype rtension (32.6%), obesity (25.6%), smoking (11.6%), and diabetes mellitus ( 4.7%). Main Outcome Measures Blood levels were compared at baseline and after the exercise program had been completed for the following: spontaneous and phyt ohemagglutinin-induced production of interleukin 1 alpha, tumor necrosis fa ctor alpha, and interferon gamma (atherogenic cytokines), and interleukin 4 , interleukin 10, and transforming growth factor beta 1 (atheroprotective c ytokines) by blood mononuclear cells; lymphocyte phenotypes and mitogenic r esponses to phytohemagglutinin; and serum C-reactive protein levels. Results Subjects exercised for a mean of 2.5 (range, 0.3-7.4) hours per wee k. Mononuclear cell production of atherogenic cytokines fell by 58.3% (P < .001) following the exercise program, whereas the production of atheroprote ctive cytokines rose by 35.9% (P < .001). Changes in transforming growth fa ctor beta 1 and in phytohemagglutinin-induced atherogenic cytokine producti on after the exercise program were proportionate to the time subjects spent performing repetitive lower-body motion exercises (P < .02), indicating a dose-response relationship. After the exercise program, changes in cellular function were reflected systemically by a 35% decrease in serum levels of C-reactive protein (P = .12). Conclusions Our data suggest that long-term exercise decreases the atheroge nic activity of blood mononuclear cells in persons at risk of developing is chemic heart disease. This may be a mechanism whereby physical activity pro tects against ischemic heart disease.