Presentation on theme: "Short-term increase in plasma IL-6 after downhill running is associated with increased core temperature during subsequent exercise-heat stress Matthew."— Presentation transcript:
Short-term increase in plasma IL-6 after downhill running is associated with increased core temperature during subsequent exercise-heat stress Matthew Fortes 1, Umberto Di Felice 1,2, Alberto Dolci 1, Naushad Junglee 1, Jamie Macdonald 1 and Neil Walsh 1 1 Extremes Research Group, Bangor University, Gwynedd, Wales. 2 Department of Biomedical Sciences and Technologies, University of L'Aquila, Italy. SUMMARY EXPERIMENTAL PROCEDURES INTRODUCTION We investigated the effect of prior muscle damaging exercise, and associated inflammation upon subsequent thermoregulation during exercise in the heat. Exercise-induced muscle damage (EIMD) increased heat storage during a subsequent heat stress test (40 min running in 33ºC, 50%RH) compared with control treatment, such that final rectal temperature was 0.5ºC higher. The greater inflammatory response following EIMD, as measured by circulating interleukin (IL)-6 was positively associated with heat storage (r = 0.58), and final core temperature (r = 0.67) during subsequent exercise heat stress. With informed consent, thirteen non-heat-acclimated healthy males (mean age ± SD, 20 ± 2 years) completed two, randomised and counterbalanced treadmill running trials separated by two-weeks. Participants performed a treatment which involved running for 60 min at 64% VO 2max at room temperature; on one occasion on a -10% gradient (EIMD), and another on a +1% gradient (CON). The running speed to elicit 64% VO 2max on both trials was verified during preliminary testing. Following both treatments, participants rested for 30 min, timed to coincide with elevated circulating inflammatory mediators, and then performed 40 min exercise heat-stress (HS) at the predetermined running speed to reflect 65% VO 2max (9.8 ± 1.2 km/h) (Fig 1). Athletes and military personnel undergoing heavy training are often expected to perform repeated bouts of arduous physical activity in the same day, often in hot environments. It has been shown that prior muscle injury may alter thermoregulation during subsequent exercise heat-stress (Montain et al. 2000). However, it remains unclear whether the acute inflammatory response that follows muscle damaging exercise (e.g. increase in circulating pyrogen IL-6) increases heat storage during subsequent exercise-heat stress. Using anti-IL-6 antibodies in rodents, a role for circulating IL-6 in the febrile response via the cyclo-oxygenase (COX) - 2 pathway has been identified (Rummel et al., 2006). The use of COX inhibitors in humans suggests that prostaglandin-mediated inflammatory processes may also contribute to rises in core temperature during exercise (Bradford et al., 2007). As such, we tested the hypothesis that acute inflammation following EIMD, using a downhill running model, increases core temperature during subsequent endurance exercise in the heat. CONCLUSIONS REFERENCES Bradford, C.D. et al. (2007). Exercise can be pyrogenic in humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 292: R143-R149. Montain, S.J. et al. (2000). Impact of muscle injury and accompanying inflammatory response on thermoregulation during exercise in the heat. J. Appl. Physiol. 89: Rummel et al. (2006). Circulating interleukin-6 induces fever through a STAT3-linked activation of COX-2 in the brain. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291: R1316-R1326. ACKNOWLEDGEMENTS We would like to thank the following people for their valuable assistance during data collection: Michael Crockford, Liam West, Ryan Hillier- Smith, Lindsey Jankowski, Megan Butterworth, Ben Terzza, Daniel Kashi, Tom Riddle and Dominique Mauger. We are also indebted to the participants for their time and co-operation. RESULTS Fig 6. Scatterplots between the difference in plasma interleukin (IL)-6 concentration between EIMD and CON, with the change in T re response between trials during exercise heat stress (A), and with the difference between trials in the final T re attained after exercise heat stress (B). n = 13. Plasma creatine kinase activity (253 ± 76 vs. 133 ± 70 U/L) and DOMS (52 ± 15 vs. 17 ± 9mm) were both greater on EIMD than CON 24-h following treatment (P<0.001). Plasma IL-6 concentration was not different between trials at baseline, but was greater on EIMD than CON immediately pre (P<0.05), and post HS (P<0.01, Fig 2). T re was significantly greater during HS on EIMD from 16 min onwards during HS (Fig 3) resulting in a 0.5 C higher final T re (P<0.01). Heat storage throughout HS was also greater following EIMD (P<0.01, Fig 4). There was no difference in mean T sk during HS between trials (P=0.38). The rapid increase in local forearm sweat rate occurred at a higher T re following EIMD, with no difference in sweat sensitivity from 6-40 min during HS between trials (Fig 5). The acute inflammatory response after treatment, measured as the difference in plasma IL-6 response between EIMD and CON, correlated well with the difference between trials in the ΔT re during HS (r=0.58, P<0.05), and with the final T re during HS (r=0.67, P< 0.05, Figs 6A & B). Mean VO 2 during HS was greater on EIMD than CON (3.0 ± 0.3 vs. 2.8 ± 0.3 L/min, P<0.01). Despite this decreased economy, the difference in VO 2 between trials did not correlate well with the difference between trials in the ΔT re during HS (r=0.24, P=0.43) nor the final T re (r=0.40, P=0.17). These data show that a bout of exercise-induced muscle damage, evoked by downhill running, increases the short-term plasma IL-6 response to exercise; and that this is associated with increased core temperature during subsequent exercise in the heat. Increased plasma IL-6 following exercise-induced muscle damage accounted for a larger proportion of variance in heat storage and final rectal core temperature during subsequent exercise heat stress, than altered economy. These results have practical relevance for athletes and soldiers undertaking multiple bouts of heavy exercise with an eccentric component in the heat. Rectal core temperature (T re ), skin temperature (4 sites, T sk ), oxygen uptake (Douglas bag method, VO 2 ), and local forearm sweat rate (ventilated capsule) were measured throughout HS. Blood samples were collected prior to treatment (baseline), and immediately pre and post HS, and assessed for plasma IL-6 concentration by ELISA (R&D systems, USA). Muscle damage was assessed 24-h post treatment by plasma creatine kinase activity and delayed onset of soreness (DOMS) by 100mm visual analogue scale. Data were analysed using ANOVA, paired t-tests and Pearson’s correlations. The study was approved by the departmental ethics committee. Fig 1. Schematic of experimental procedures (EIMD, exercise-induced muscle damage). Fig 3. Rectal core temperature (T re ) responses to exercise heat stress (HS) performed 30 min after either exercise-induced muscle damage (EIMD) or control exercise (CON). **P < 0.01 vs. time 0; # P < 0.05, and ## P < 0.01 between trial differences. n = 13. Fig 4. Heat storage (Δ T re ) during HS performed 30 min after either exercise-induced muscle damage (EIMD) or control exercise (CON). ## P < 0.01 between trial difference. n = 13. Fig 5. Mean local forearm sweat rate as a function of T re during HS performed 30 min after either exercise-induced muscle damage (EIMD) or control exercise (CON). n = 11. Fig 2. Plasma IL-6 response at baseline, and pre and post exercise heat stress (HS). HS was conducted 30 min after either exercise-induced muscle damage (EIMD) or control exercise (CON). **P < 0.01 vs. baseline; # P < 0.05, and ## P < 0.01 between trial differences. n = 13.