Prolonged bouts of exercise and periods of chronic training induce transient immune perturbations, but the clinical relevance of these changes remain questionable with the majority of work relying on in vitro measures of immunity. As such, there is a need to utilise in vivo measures of immunity that likely relate better to infection than in vitro measures because they extend beyond isolated blood measures and involve whole-body integrated immune responses. Sensitisers such as diphenylcyclopropenone (DPCP) induce cutaneous responses by the activated chemical specific T-cells upon first exposure that require a period of time for the formation of ‘immune memory’ resulting in a boosting of responses upon re-exposure. As such, DPCP may provide an attractive tool for scientists to examine the influence of stressors on in vivo T-cell mediated immunity that allows control over the timing of initial exposure in relation to stressors. Indeed, decreases in contact hypersensitivity (CHS) responses to DPCP induction after prolonged exercise have previously been shown (Diment et al., 2015; Harper Smith et al., 2011). However, irritant properties of the antigen may influence the sensitising potential, and it remains unknown whether the influence of stressors on in vivo immunity to DPCP reflect localised responses at the skin mediated primarily by localised irritant properties or reflect a systemic in vivo immune response. In addition, there is strong supporting evidence that DPCP responses relate to clinical outcomes in immune deficient populations, but the association with regard to upper respiratory illness (URI) in otherwise healthy populations remains to be determined.
Psychoneuroimmunologists have long since acknowledged the role of psychological stress on immunity, with psychological factors likely playing a role in the decrease in immunity with prolonged heavy exercise and heavy training. However, empirical evidence supporting this notion is lacking and there is a need to bridge the gap between exercise immunology and psychoneuroimmunology by examining the role of psychological factors on exercise-immune modulation. With this information in mind, the broad aim of this thesis was to examine the role of anxiety and psychological stress on the in vivo immune response, and investigate their role in exercise-immune modulation, and examine the clinical relevance of DPCP with regard to URI.
Firstly, we demonstrated no influence of prolonged exercise stress on local cutaneous processes to a local irritant (croton oil), supporting the notion that the previously observed decrease in CHS responses to DPCP induction after prolonged exercise likely represents a systemic suppression of in vivo immunity (Chapter 4). We then re-interrogated our previous data which examined the influence of exercise intensity and duration on in vivo immunity, and found that low-moderate levels of state-anxiety and perceived psychological stress before exercise play an important role in determining the strength of the in vivo immune response after exercise, irrespective of the intensity and duration (Chapter 5). We next sought to determine the role of low, moderate and high levels of anxiety prior to an acute psychological stressor on in vivo immunity, and observed that the DPCP response was lower in those reporting low and high anxiety, supporting an inverted-U association between the a priori level of anxiety and the in vivo immune response after an acute psychological stressor (Chapter 6). We then demonstrated lower DPCP responses during a common cold (Chapter 7), and prospectively showed an association between DPCP responses and URI, whereby, the CHS response to DPCP induction was a significant predictor of peak URI severity, and lower CHS responses were observed in those who reported more severe URI episodes compared with those reporting less severe URI episodes. Moreover, low DPCP responders reported more severe URI episodes, longer total URI duration and greater total URI symptom scores compared with high DPCP responders (Chapter 8). Taken together, these findings provide promising preliminary support for the clinical utility of experimental CHS using DPCP.
In conclusion, the findings of this thesis highlight the salient role of psychological factors on in vivo immunity, and their role on exercise-immune modulation, and provide promising initial support for the use of DPCP as a clinically relevant measure of in vivo immunity. The findings within this thesis support the recommendation that exercise scientists account for anxiety and psychological stress when examining the immune response to exercise, and that exercise immunologists and psychoneuroimmunologists are encouraged to utilise in vivo measures of immunity such as experimental CHS using DPCP.