Loughborough University
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Strategies to induce an inflammatory response: a focus on alternatives for people restricted to engage in lower-body exercise

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posted on 2019-02-06, 12:32 authored by Sven P. Hoekstra
INTRODUCTION. Chronic low-grade inflammation is increasingly recognised as a risk factor for non-communicable diseases such as type 2 diabetes mellitus and cardiovascular disease. Regular exercise has a protective effect against these type of diseases, possibly partially resulting from the acute inflammatory response and the subsequent anti-inflammatory milieu created following each bout of exercise. This acute response is characterised by an increased production of interleukin (IL)-6, heat shock protein 72 (Hsp72), and anti-inflammatory cytokines such as IL-1ra and IL-10. However, engaging in exercise of sufficient volume to induce an acute inflammatory response may not be feasible for those who are restricted to be physically active. In this thesis, factors that may influence the acute inflammatory response to exercise are investigated to inform strategies to reduce chronic low-grade inflammation in people with a low physical capacity. Furthermore, the efficacy of 2 such strategies, namely upper-body high-intensity interval training (HIIT) and hot water immersion (HWI), to induce an acute inflammatory response is investigated. Moreover, the effect of a chronic HWI intervention on the inflammatory profile and metabolic markers at rest is assessed. METHODS. In Chapters 2 and 3, factors that may influence the acute inflammatory response to exercise are investigated. The impact of chronic, modality-specific training adaptations and active muscle mass is investigated in individuals chronically trained in either upper- or lower-body exercise, while the role of autonomic function is studied in wheelchair athletes taking part in a wheelchair half-marathon. Thereafter, studies exploring the efficacy of relatively novel health promoting strategies to improve the inflammatory profile are presented. The acute increase in IL-6 and IL-1ra concentrations following upper-body HIIT is compared with moderate-intensity upper-body exercise in Chapter 4. In Chapters 5 and 6, the acute and chronic effects of HWI on inflammatory and metabolic markers in sedentary overweight males are studied. Finally, an in-vitro model is used to gain more insight in the potential of temperature elevations to induce an acute inflammatory response in monocytes (Chapter 7). The main inflammatory markers investigated in the present thesis are IL-6, intracellular Hsp72 in monocytes, extracellular Hsp72 and the distribution of monocyte subsets. Alongside the inflammatory markers, perceptual responses are collected to help inform the implementation of the studied interventions. RESULTS. Chronic modality-specific training adaptations, the reduced active muscle mass and autonomic dysfunction have all shown to attenuate the acute inflammatory response following upper-body exercise. Although HIIT did not result in a larger acute increase in plasma IL-6 and IL-1ra concentrations, it was more time efficient and perceived as more enjoyable than moderate-intensity continuous exercise. A single HWI session induced an acute elevation in plasma IL-6 concentration, as well as a shift in the monocyte subset distribution. However, this was not accompanied by an increase in iHsp72 expression. A higher core temperature than observed in Chapter 5 (38.7±0.4℃) may be needed to increase iHsp72 expression; which was supported by the results of Chapter 7, where incubation of whole blood at 40℃ but not 38.5℃ increased iHsp72 expression in monocytes. A chronic 2-week HWI intervention reduced fasting glucose and insulin as well as eHsp72 concentrations at rest. No change in resting IL-6 or iHsp72 was observed following the intervention. CONCLUSION. The observation that a range of factors can reduce the potential of exercise to induce an acute inflammatory response in people restricted to engage in (lower-body) exercise may warrant additional health promoting strategies to reduce chronic low-grade inflammation in these individuals. The results of the present thesis support the potential of body temperature manipulations to be such a strategy. The lowering of fasting glucose and insulin, as well as eHsp72 following a relatively short-term chronic HWI intervention suggest that passively increasing body temperature may be a viable tool to improve the inflammatory profile and metabolic health in people restricted to be physically active.


Loughborough University, School of Sport, Exercise and Health Science.



  • Sport, Exercise and Health Sciences


© S.P. Hoekstra

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This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/

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A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy of Loughborough University.


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