Circulatory Endotoxin Concentration and Cytokine Profile During Multi-Stage Ultra-Marathon Competition Conducted in a Hot Ambient Environment.


Gastrointestinal distress is a commonly reported feature of prolonged physical exertion in the heat. Indeed, exertional-heat stress has the potential to disturb the integrity of gastrointestinal mucosal structures, potentially leading to increased intestinal permeability of enteric microorganisms and associated clinical manifestations (e.g. endotoxaemia, cytokine induced pyrogenesis and heat stoke). This observational study aimed to determine changes in circulatory endotoxin concentration and cytokine responses during a 230km multi-stage ultra-marathon (MSUM) conducted over five days in hot ambient conditions (32 to 40ºC) and routed over arid undulating terrain. Body mass, tympanic temperature and venous blood samples were taken from ultra-endurance runners (UER, N=19) and control non-runners (CON, N=12) before and immediately after each stage of the MSUM. Aliquots of plasma were used to determine plasma osmolality by freezepoint osmometry, endotoxin by LAL chromogenic endpoint assay, CRP and cytokine profile by ELISA. Gastrointestinal symptoms were monitored each day along the MSUM. Data was analysed using ANOVA with post hoc Tukeys. Significance was accepted as p<0.05. Stage mean body mass loss ranged between 1.0% to 2.5%. Pre- and post-stage tympanic temperature was within normal range in all UER. Overall mean pre- and post-stage plasma osmolality in UER was 277±15mOsmol/kg and 293±14mOsmol/kg, respectively. Pre- to post-stage increases (17%) in plasma endotoxin concentration were observed in 89% of UER (p=0.005). Pre- and post-stage plasma CRP concentration in UER increased by Stage 2 (5.8 and 4.6-fold, respectively; p<0.001) and remained elevated throughout the MSUM. In UER, plasma concentrations of IL-6 were higher pre-Stages 2 and 3 (p=0.036), IL-1β and IL-1ra were higher pre-Stages 2 to 5 (p<0.001), TNFα and IFNγ were higher pre-Stages 3 to 5 (p=0.013 and p=0.002, respectively), compared with pre-Stage 1. Pre-stage plasma concentrations of CRP, IL-6, TNFα and IL-10 were higher in UER than CON along the MSUM (p<0.05). Pre- to post-stage increases in IL-6 (37%, p=0.008), IL-1β (14%, p=0.003), IL-1ra (58%, p<0.001), TNFα (18%, p=0.083) and IFNγ (13%, p=0.065) were observed in UER. Incidences of gastrointestinal distress were reported by 92% of UER along competition. MSUM competition in the heat resulted in significantly increased pro-inflammatory immune responses, which may have been exacerbated by the modest rise in circulatory endotoxin concentration. It is likely that thermoregulatory management and maintenance of euhydration in the majority of UER contributed to attenuating further exacerbation of these responses. Contrary to previous literature, no associations between gastrointestinal distress and blood parameters measured were observed.

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