آسیب پذیری، پریشانی‌ و واکنش ایمنی در مقابل واکسیناسیون در بزرگسالان مسن تر

Psychological distress and biobehavioral vulnerability (e.g., arising from being older or sedentary) have independently predicted immune responses to influenza vaccination in older adults. Recent research examining basal inflammatory markers suggests that, rather than having additive effects, distress and vulnerability interact with each other. The present study tested the interactions between distress and age, sex, education, BMI, sleep quality, and physical activity over up to 8 years in older adults (N = 134; M age = 74 years) who received annual influenza vaccinations. Measured vaccination responses were changes from baseline in antibody to the three vaccine components, interleukin (IL)-6, and β2-microglobulin. As predicted, the most robust effects were interactions between distress and vulnerability. BMI interacted with stable individual differences in distress to predict antibody response (t(132) = 3.09, p < 0.003), such that only the combination of low BMI and low distress was associated with a more robust antibody response. Likewise, changes in physical activity over time interacted with changes in distress (t(156) = 2.96, p < 0.004), such that only the combination of increased physical activity and decreased distress was associated with a more robust antibody response. Finally, there was a smaller tendency for age to interact with stable individual differences in distress (t(130) = 2.46, p < 0.015), such that distress was more strongly associated with post-vaccination IL-6 at older ages. The synergistic effects of distress and other forms of vulnerability are an important direction for future research and a target for interventions to improve immunological health in older adults.

Vaccination against influenza in older adults has the potential to provide protection against negative health consequences, including hospitalizations and deaths. However, many older adults do not mount robust antibody responses to the vaccine. When antibody production following vaccination is low, the individual may still be vulnerable to infection and the negative health consequences thereof (Gardner et al., 2001, Hannoun et al., 2004 and Webster, 2000). In addition, antibody responses are not the only immune response to vaccination. Vaccination can also induce inflammatory responses. Most side effects of influenza vaccination are related to inflammatory responses, from minor, local responses such as pain to more serious systemic responses such as fever, neuritis, and myelitis. Inflammatory and acute phase responses to vaccination are often transient and last only a matter of days, but there are large individual differences in degree of response, with some people showing increases in inflammatory markers and others, decreases. Furthermore, individual differences – including psychological factors – also affect duration of response, such that increases in inflammatory markers may be evident weeks after vaccination in some people (Bernstein et al., 1998, Carty et al., 2006, Glaser et al., 2003, Segerstrom et al., 2008, Trzonkowski et al., 2004 and Tsai et al., 2005). Changes in antibody and inflammatory markers after vaccination are independent of each other (Bernstein et al., 1998 and Krakauer and Russo, 2001). Stress and distress have been associated with both poor antibody responses and higher inflammatory markers in older adults. For example, studies of dementia caregivers have found that caregiving is associated with lower antibody response and, in some cases, higher IL-6 after vaccination (Kiecolt-Glaser et al., 1996, Segerstrom et al., 2008 and Vedhara et al., 1999). However, some people may be more immunologically sensitive to the negative effects of stress and distress than others. In studies of healthy middle-aged and older adults, various measures of psychosocial well-being or distress were more strongly related to basal markers of systemic inflammation in women, those who slept poorly, those who did not engage in moderate-intensity physical activity, and those with less education (Friedman et al., 2005, Morozink et al., 2010, Morris et al., 2011, Rethorst et al., 2011 and Steptoe et al., 2008). Synergistic effects of distress and demographic and behavioral variables may explain why some studies have not found main effects of stress or distress on antibody responses to vaccine (e.g., Moynihan et al., 2004). Other qualities that may increase vulnerability include older age and higher BMI. Even within older age, aging is associated with poorer antibody responses to vaccination and higher basal markers of systemic inflammation (Goodwin et al., 2006 and Harris et al., 1999). Higher BMI is associated with higher markers of systemic inflammation, particularly IL-6, due to the presence of active macrophages in adipose tissue, particularly in visceral fat (O’Connor et al., 2009). Therefore, older age and higher BMI may also predispose to higher inflammatory and activation markers after vaccination. The present study used data from a longitudinal study of psychosocial factors and immunological responses to vaccination in older adults to test the combinations of demographic and behavioral vulnerabilities with psychological distress as predictors of antibody to vaccine components, as well as markers of immune activation and inflammation (β2 microglobulin (β2μ) and interleukin (IL)-6). β2μ is an element of the major histocompatibility complex shed primarily by activated lymphocytes. It is elevated in serum during infection and inflammation, correlates with C reactive protein during influenza infection, and is found in higher levels in serum in healthy older compared with younger adults (Cooper et al., 1984 and Zissis et al., 2001). IL-6 is a pleiotropic cytokine involved in the inflammatory cascade and produced by many somatic cells; it is also elevated during inflammation and correlated with C reactive protein (Papanicoloau et al., 1998). We hypothesized that the effects of stress and distress would interact with vulnerability factors to predict undesirable immunological outcomes after vaccination (lower antibody response and higher inflammatory and activation markers). With regard to vulnerabilities, we tested a set of stable demographic vulnerabilities that included age, gender, education, and BMI, and a set of time-varying behavioral vulnerabilities that included physical activity and sleep quality. The specific hypotheses were as follows: 1. Antibody and inflammatory and activation marker changes after vaccination are independent of each other. 2. Vulnerability to undesirable immunological outcomes after vaccination will be associated with older age, female gender, less education, high BMI, poor sleep quality, and low physical activity. Each of these characteristics has predicted undesirable immunological outcomes either alone or in combination with psychosocial factors. 3. The combination of distress and vulnerability will be the best predictor of such outcomes, such that distress is more strongly related to undesirable outcomes among vulnerable individuals.