There is compelling evidence that emotions may influence immune system function and thus susceptibility to and severity of immune-related diseases (Glaser and Kiecolt-Glaser, 2005). This body of research has traditionally focused on negative affective states—such as depression, anxiety, and anger (Kiecolt-Glaser et al., 2002 and Raison et al., 2006). However, there is growing interest in how positive psychological factors—such as positive affect, optimism, and benefit finding—affect health (Pressman and Cohen, 2005 and Bower et al., 2008b) and the immunological pathways through which they exert their effects (Marsland et al., 2007).
To date, positive affect is the most commonly studied positive psychological factor relating to health and immune outcomes. For example, research has shown that positive affect predicts lower risk of HIV-related mortality (Moskowitz, 2003), enhanced antibody response to Hepatitis B vaccination (Marsland et al., 2006), decreased susceptibility to experimentally-exposed rhinovirus/influenza A virus (Cohen et al., 2006), fewer objective and subjective signs of illness following viral exposure (Doyle et al., 2006), and faster skin wound healing (Robles et al., 2009). In the context of viral challenge, higher levels of positive affect are associated with lower levels of nasal proinflammatory cytokines, which appear to mediate effects on illness symptoms (Doyle et al., 2006 and Janicki-Deverts et al., 2007). Effects of positive affect on these outcomes appear to be independent of, and in some cases, stronger than effects of negative affect (Cohen et al., 2006, Janicki-Deverts et al., 2007, Prather et al., 2007 and Robles et al., 2009).
Naturalistic studies have shown more equivocal associations between positive affect and inflammatory markers. One such study found no association between positive affect and the soluble IL-6 receptor (sIL-6r) in healthy older women, but did find a positive association between eudemonic well-being (i.e. purpose in life) and sIL-6r (Ryff et al., 2004). A large longitudinal study of 2873 healthy adults found that positive affect was associated with lower circulating levels of C-reactive protein (CRP) and IL-6 for women, but not for men (Steptoe et al., 2008). Another study also found a negative association between positive affect and stimulated production of IL-6 and IL-10, but not IL-1β or TNF-α (Prather et al., 2007).
To date, studies of positive affect and inflammation have primarily focused on healthy populations. However, inflammatory processes may have particular relevance in the context of cancer, as inflammation is increasingly recognized as a contributor to cancer development and progression (Coussens and Werb, 2002 and Shacter and Weitzman, 2002) and may also play a role in cancer-related symptoms such as fatigue (Bower, 2008). In women with advanced ovarian cancer, positive psychological factors such as social support have been linked to lower levels of circulating IL-6 and VEGF, a cytokine involved with tumor angiogenesis (Costanzo et al., 2004 and Lutgendorf et al., 2002). In contrast, depression is associated with elevations in proinflammatory cytokines in cancer populations (Jehn et al., 2006, Lutgendorf et al., 2008 and Musselman et al., 2001).
To our knowledge, positive affect has not been examined in relation to inflammatory cytokines in cancer patients. We choose to examine this relationship among breast and prostate cancer patients undergoing radiation therapy. Radiation is a mainstay of cancer treatment, and works by interfering with tumor growth and metastasis by damaging the DNA of malignant cancer cells. Radiation therapy activates proinflammatory cytokine production as part of a coordinated response designed to control damage and promote tissue repair (Petrini et al., 1992, Barcellos-Hoff, 1998, Stone et al., 2003 and Okunieff et al., 2008). To the extent that proinflammatory cytokines facilitate tissue recovery, increases in cytokine concentrations during treatment should have beneficial effects for patients undergoing radiation therapy. Indeed, acute wound healing studies have found that higher levels of IL-1β and IL-6 at the wound site are associated with faster wound healing (Kiecolt-Glaser et al., 2005). However, radiation-induced elevations in proinflammatory cytokines may also have detrimental effects. For example, elevations in circulating levels of IL-6 predicted the development of radiation pneumonitis in lung cancer patients and acute proctitis in prostate cancer patients (Arpin et al., 2005, Hartsell et al., 2007 and Christiansen et al., 2007). Cytokine activation might be particularly problematic if it persists beyond treatment completion, suggesting more chronic inflammation.
The current study was designed to test the association between positive affect and inflammation among breast and prostate cancer patients undergoing radiation treatment. Primary analyses focused on two key proinflammatory cytokines—IL-1β and IL-6—that are known to be elevated during radiation therapy and have previously been associated with positive affective processes (Ryff et al., 2004, Prather et al., 2007 and Steptoe et al., 2008). To investigate the impact of positive affect on inflammation, we examined whether individuals who reported higher levels of positive affect prior to treatment onset showed a differential cytokine response to treatment. To clarify the clinical significance of this response, we examined treatment-related side effects and followed patients after treatment completion.
