The exercise-induced enhancement of influenza immunity is mediated in part by improvements in psychosocial factors in older adults
Introduction
Older adults experience a greater mortality rate from influenza infection and generally exhibit reduced vaccine efficacy (Keren et al., 1988, Lui and Kendal, 1987, Sprenger et al., 1993). Among persons over age 65 hospitalized for influenza, 58–61% had been previously vaccinated (Betts and Treanor, 2000, Falsey et al., 1995). Vaccine efficacy estimates for older adults range from 31 to 65% in preventing influenza (Gross et al., 1995), whereas vaccine efficacy ranges from 68 to 88% in younger adults (Demicheli et al., 2000, Wilde et al., 1999).
A significant number of older adults may not develop protective antibody titers (defined as hemagglutination inhibition HI ⩾ 40) after immunization (Davis and Grillis, 1989, Keren et al., 1988). Upon infection, cytotoxic T cells (CTL) are important in viral clearance (Bender et al., 1991, McMichael et al., 1983). However, CTL response to influenza viral infection is also impaired among older adults (Mbawuike et al., 1993, Powers, 1993). Age-related changes in cytokine balance may impact resistance to infection (Shearer, 1997), and younger adults produce greater amounts of interleukin-2 (IL-2) and interferon-γ (IFNγ) post-vaccination than older adults (Bernstein et al., 1998, McElhaney et al., 1990, McElhaney et al., 1998). Ultimately, optimal defense against viral infection in older adults may be dependent on several factors: (1) the ability to mount an effective CTL response, (2) generation of antibody, and (3) production of appropriate cytokines (e.g., IFNγ to enhance CTL; Yamada et al., 1986). Therefore, the immune parameters measured in this investigation included antibody titer, as a measure of vaccine efficacy, and influenza-specific IFNγ, a cytokine important in driving CTL.
One of the strategies to improve immunocompetence among older adults is moderate exercise (Kohut et al., 2002, Shinkai et al., 1995, Woods et al., 1999). Exercise may enhance immunity through the release of neuroendocrine factors that bind to and alter immune cell function (Pedersen and Hoffman-Goetz, 2000). Alternatively, exercise may enhance immunity indirectly by reducing depression or improving mood, thereby attenuating the negative influence of psychosocial factors on immunocompetence. Exercise reduces depression, anxiety, and alters mood (Arent et al., 2000, Blumenthal et al., 1999, Dunn et al., 2001). Associations between stress, depression, and anxiety with immune responsiveness are also well documented (Kiecolt-Glaser et al., 2002, Zorrilla et al., 2001), and therefore it is plausible that an exercise-induced alteration of psychosocial variables may influence immunocompetence. Depression is measured in this study as a factor that may negatively impact immunity, whereas sense of coherence is measured as a factor that may positively affect immune response.
The purpose of this study was to determine whether improvements in immune response resulting from a long-term (10 month) exercise intervention are mediated by improvements in psychosocial factors in older adults. We hypothesized that an exercise-induced increase in immune response (antibody titer, IFNγ) would be mediated by improvements in psychosocial factors (depression, sense of coherence). A better understanding of how exercise attenuates the age-related decrement of immune function will provide us with insights concerning how to advise the elderly on enhancing resistance to infection via psychological or physiological means.
Section snippets
Participant screening, enrollment, and randomization
Older adults were recruited from the local Ames, IA community through the placement of advertisements. All procedures involving human subjects were approved by the Institutional Review Board for Human Subjects at Iowa State University. Participant inclusion and exclusion were dependent on age, health status, independent living status, medication and supplement use, influenza vaccine history, and ability to perform aerobic exercise. Health status was determined by a detailed medical history,
Effect of exercise intervention on health, fitness, and psychosocial variables
Prior to the intervention, differences did not exist on the health/fitness variables between the exercise and control group (see Table 2). After the 10-month exercise intervention, a significant main effect of time (p < .05) was observed with respect to diastolic blood pressure, F (1, 25) = 4.64, p = .041, and 6 min walk distance, F (1, 25) = 35.81, p < .001. However, a significant time by treatment interaction [F (1, 25) = 13.49, p = .001] was also observed with respect to the 6 min walk distance, such that the
Discussion
The purpose of this study was to determine whether exercise-induced alterations in the immune response to influenza immunization were mediated by improvements in psychosocial factors. The exercise treatment condition was associated with a greater increase in antibody titer to the influenza vaccine. However, the improvement in depression scores and sense of coherence did not mediate this increase in antibody titer. In contrast, the improvements in depression scores and sense of coherence did
Acknowledgment
This work was supported in part by a grant from NIAID, No. R01 AI49956.
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