This study is the first to identify a relationship between positive affect and treatment-related changes in proinflammatory cytokines among early-stage breast or prostate cancer patients undergoing radiation therapy. In particular, we found that positive affect was associated with higher circulating levels of IL-1β and IL-6 during radiation treatment in breast and prostate cancer patients.
This finding may seem counterintuitive, since previous studies conducted with healthy individuals have shown either no relationship or an inverse relationship between positive affect and markers of inflammation (Ryff et al., 2004
; Prather et al., 2007
; Steptoe et al., 2008
). In these populations, inflammation is generally considered to have negative consequences for future health, given its association with cardiovascular disease (Cesari et al., 2003
), type-2 diabetes (Pradhan et al., 2001
), and all-cause mortality (Harris et al., 1999
). However, among cancer patients undergoing radiation therapy, the health implications of cytokine elevations are unclear. Radiation activates proinflammatory cytokine production as part of a coordinated response designed to control damage and promote tissue repair. Thus, increases in cytokine levels during treatment may have beneficial effects on tissue recovery, similar to effects seen in acute wound healing studies (Kiecolt-Glaser et al., 2005
Ultimately, we hypothesize that radiation-induced elevations in proinflammatory cytokines may be a double-edged sword, with effects depending on the timing and level of their expression (Wyss-Coray and Mucke, 2002
; Hagemann et al., 2007
). Inflammatory responses may be adaptive if they are circumscribed and time-limited, but may have detrimental effects if they are too large, occur too frequently, or remain elevated over time. In one study with lung cancer patients, development of radiation toxicity was predicted by mean baseline IL-6 levels of 15.7 pg/ml (vs. 7.6 pg/ml in patients who did not) (Arpin et al., 2005
). Baseline IL-6 levels in our sample (mean = 4.03 pg/ml, median = 2.66 pg/ml) fell well below this range, and subsequent elevations in IL-6 levels returned to baseline levels after completion of treatment. Further, increases in IL-1β and IL-6 were not associated with skin toxicity, a common side effect of radiation exposure in breast and prostate cancer patients. These results suggest that the circumscribed elevations in proinflammatory cytokines associated with positive affect in this study are unlikely to have detrimental effects on health, and may instead facilitate the tissue healing process.
Our study was not designed to identify the mechanisms through which positive affect is associated with inflammation, and thus pathways remain speculative. It was notable that the majority of our participants reported feeling happy, hopeful, and enjoying life “most or all of the time” at treatment onset, suggesting that high levels of positive affect were the norm in this sample. Similar high levels of positive affect on the CES-D have been observed in other, larger samples (Moskowitz et al., 2008
). If high positive affect is indeed normative, another interpretation of our results is that positive affect does not necessarily enhance the inflammatory response to radiation treatment, but rather that a deficiency
in positive affect may dampen an otherwise healthy response. This hypothesis is in line with research that suggests that positive affect is associated with enhanced allostasis–buffering against the negative effects of stress and promoting restorative physiological systems (Bower et al., 2008
). In the context of radiation therapy, positive affect may buffer against cancer and treatment-related stressors that dysregulate normal inflammatory response.
The primary limitation of this study was the small sample size. Given variability in cytokine levels during treatment, future studies may need larger sample sizes to increase the reliability of findings. In addition, although our assessment schedule was relatively intensive, more frequent sampling of cytokine levels may be required to fully capture the dynamic changes in cytokine production that occur during radiation therapy and to more accurately characterize the timing and duration of cytokine elevations. We also did not precisely control for time of blood draws, although the majority of samples were collected in the morning. Furthermore, a longer post-treatment follow-up would provide critical information about the association between positive affect and persistent inflammation. Finally, because we did not utilize an experimental design, we cannot draw conclusions about direction of causality. However, since positive affect was assessed before the onset of radiation therapy, it is unlikely that radiation-induced cytokine elevations drove positive affect, rather than vice versa.
Our results, though preliminary, suggest that positive affect is associated with changes in the inflammatory response to radiation treatment. These findings may have relevance for tissue repair processes. The importance of positive affect for inflammation, both in acute and chronic settings, merits focused attention in future research.