The Inflammatory Profile Of Post Hip Fracture Females

Published Date: 02 Nov 2017

5.4- Discussion

The major finding of this study was that completion of a 12 week moderate intensity chronic resistance exercise programme significantly improved the inflammatory profile of post hip fracture females, demonstrating significant decrements in TNFα alongside improvements in IL-10. Healthy females reported decrements in TNFα, whilst increasing IL-6 and IL-10 following chronic exercise, although no significant interaction was demonstrated. Increases were observed in all muscle strength markers following chronic exercise, in addition to being conducted with high compliance and adherence. This study demonstrates that a home based Theraband resistance programme is not only feasible for recovering post hip fracture females but can also elicit strength improvements for healthy older females. Chronic exercise also improved the acute response to exercise in healthy females, documenting a significant increase in IL-10 and meaningful in TNFα between the first and second acute resistance phase. Contrastingly post hip fracture females experienced marked decrements in all cytokines following acute resistance exercise. Although completion of chronic exercise appeared to work towards an attenuation of this response, the present study demonstrates that post hip fracture females respond differently to acute resistance exercise in direct comparison to healthy older females, but that this is amenable to change following exercise.

In the present study the predominant aim was to establish the chronic effects of resistance training, however ascertaining the acute response to resistance exercise is also important, this was highlighted in the current study findings. Conflicting responses were documented following both acute and chronic exercise for post hip fracture and healthy females, suggesting that a high level of cross talk exists between the adaptive mechanisms of acute and chronic exercise (Gleeson et al., 2011). Thompson et al., (2000) advocated that acute and chronic responses should not be regarded as two separate entities. Hawley et al., (2006) suggested the concept that chronic exercise adaptations result from the accumulation of transient events occurring during acute bouts of exercise and in the period of recovery following exercise, resultantly evoking a compensatory cellular and molecular response (Pederson et al., 2006; Mathur et al., 2008; Brandt & Pedersen, 2010; Woods et al., 2011). Inflammatory changes observed in the post hip fracture group support this whereby chronic exercise decreased IL-6 and TNFα within post hip fracture females, whilst also improving IL-10. Demonstrating that completion of exercise on a regular basis over a period of time, improved anti-inflammatory markers, combined with decreased pro-inflammatory markers (Bruunsgaard et al., 1999; Pederson et al., 2006; Peake et al., 2010). However it is important to note that whilst both groups demonstrated improved inflammatory profiles following chronic exercise, differential trends were observed following acute resistance exercise. In consideration of the fact that inflammatory pathways are synonymously activated following an acute bout of exercise, it is perhaps contradictory that results demonstrated decreased markers of inflammation following chronic exercise (Ploger et al., 2009; Nicklas & Brinkley, 2009). In essence it is the respective combination and magnitude of these alterations which determine the adaptation that will take place, whether the end state is increased catabolism, protein synthesis or muscle damage (Nicklas & Brinkley, 2009). It is plausible that post hip fracture females were unable to sustain a normal prescribed acute response to resistance exercise (Evans, 2010). Although the precise link between acute and chronic exercise has not been unanimously clarified for this age group (Brandt & Pedersen, 2010), the results from this study demonstrate alternate responses to both acute and chronic exercise, potentially suggesting a form of dysregualtion within the inflammatory response for post hip fracture group (Beavers, Brinkley & Nicklas, 2010).

Chronic exercise improved IL-10 in addition to decreasing TNFα in both post hip fracture and healthy females, it is plausible that these results may positively contribute towards decreasing high levels of inflammatory markers, combined with a heightened opportunity for recovery and repair in skeletal muscle (Pederson et al., 2006). Heightened IL-10 due to its anti inflammatory properties can work towards improving the cellular redox environment, decreasing TNFα and stabilising IL-6 (Gleeson et al., 2011). It has been postulated that IL-10 plays an important role in the orchestration of the inflammatory response, namely through macrophage and monocyte activation (Petersen & Pedersen, 2005). A number of researchers have adopted the IL-10/TNFα ratio as an indicator of inflammatory status and disease related morbidity, whereby decreased values have been associated with poorer prognoses (Kaur et al. 2006; Leonidou et al. 2007). Research has shown that chronic exercise possesses the ability to positively modify the IL-10/TNFα ratio (Petersen & Pedersen 2005; Lira et al., 2009). Results from the present study are in agreement with the work of Petersen and colleagues, (2005) following completion of chronic exercise IL-10/TNFα ratios increased from (0.12 to 0.22) in post hip fracture females and from (0.49 to 0.74) in healthy females. However post hip fracture IL-10/ TNFα ratios were significantly lower in direct comparison to healthy individuals, suggesting that post hip fracture females may be subject to increased levels of inflammatory stress, potentially contributing towards a reduced state of health and well being (Steensberg et al.., 2003).

The results demonstrate varying patterns of expression for IL-6. In the healthy group IL-6 increased slightly following chronic exercise which was not expected (6.95 ± 2.22 to 7.44 ± 6.62), whereas the post hip fracture group demonstrated decrements in IL-6. Results obtained in the current study offer alternate explanations into the role of IL-6, one offering support for its anti inflammatory properties and the other towards the pro inflammatory capabilities of IL-6 (Scheller, Schmidt- Arrad & John, 2011). Healthy controls documented increased IL-10 and lower TNFα, in addition to higher IL-6 following chronic exercise. This supports the work conducted by Febbarrio and colleagues (2004) whereby heightened IL-6 has been shown to attenuate the production of TNFα through respective inhibition of TNFα transcription, stimulating the production of anti-inflammatory cytokines such as IL-1 and IL-10 (Xing, Gauldie, Cox et al., 1998; Peterson et al., 2006; Ogawa et al., 2010). Contrastingly completion of chronic exercise negatively affected IL-6 for the post hip fracture group, documenting marked decrements in IL-6 as depicted in figure 1. It is plausible that lower IL-6 for the post hip fracture group may partially explain extremely high TNFα at the end of the 12 week chronic exercise period. Work conducted by Matthys and colleagues, (1995) offers support for this, documenting a role for IL-6 in the regulation of TNFα, whereby elevations were noted in TNFα when IL-6 production was inhibited resulting in an increased pro inflammatory environment. As IL-6 is believed to exert both pro and anti inflammatory effects, this proposes a potential link between IL-6 activation and TNFα (Pederson et al., 2006). Additionally it is plausible that elevated IL-6 reported at baseline for post hip fracture females may have been an attempt to attenuate extremely high levels of TNFα. Post hip fracture females experienced heightened TNFα values during each time point, correspondingly a significant main interaction effect was noted for TNFα pre and post chronic exercise. Due to the deleterious effects which TNFα has been shown to evoke, decreases in this pro inflammatory cytokine may be of clinical relevance (Gleeson et al., 2011). Higher concentrations of TNFα are strongly associated with many chronic diseases, decreased muscle strength and physical function (Pederson et al, 2006; Miller et al., 2006). Present findings would suggest that a moderate intensity exercise programme may help attenuate the dysregualted immune response and serve to improve individual’s overall inflammatory status.