Pre‐race Inflammatory Cytokines Are Not Consistent Predictive Biomarkers of the Magnitude of Post‐race Core Temperature Elevations at the Falmouth Road Race

Abstract

Exercise in stressful environmental conditions induces multiple independent signaling pathways that result in inflammatory cytokine release. Immune responses that cause and are driven by the systemic release of inflammatory and pyrogenic cytokines contribute to endotoxemia, sepsis, and other immunity‐related exertional heatstroke (EHS) pathophysiology. Our preliminary data from the Falmouth Road Race (FRR, 11.3 km, Falmouth, MA), a race, known to have high incidence (15–20 annually) of EHS, suggest that at least one particular pro‐inflammatory pathway stimulated by circulating lipopolysaccharide (LPS) is robustly upregulated post‐race. In this study, we aimed to test the hypothesis that competing in a high intensity running road race in a hot and humid environment will result in increased cytokine levels that may serve as biochemically downstream predictive measures of an EHS susceptibility marker, core temperature. We recruited 32 (2015), 33 (2016), and 32 (2017) subjects (43±12 years, 174.2±8.6 cm, 72.3±12.6 kg, 17.0±5.1% body fat, 43.49±8.01 mL·kg−1·min−1 VO2max) participating in the FRR. We measured environmental and physiological variables, and acquired venous blood pre (PRE) and immediately post (POST) race. We quantified six different cytokines (IL‐6, IL‐8, IL‐10, IL‐1β, TNF‐α, and IL‐12p70) in anti‐coagulant treated blood plasma (pg·ml−1). ANOVA with Bonferroni post hoc tests and Pearson correlations were calculated to determine statistically significant (p<0.05) differences in cytokine concentration and correlations between cytokine concentrations and POST gastrointestinal temperature (Tgi). POST (vs. PRE) Tgi was elevated significantly each year and for the pooled 3‐year data (mean±SD °C, PRE: 36.97±0.48, POST: 39.55±0.79, p<0.00001). Pooled (3‐year) IL‐6 (mean±SD, PRE: 29.25±17.45), IL‐10 (PRE: 18.54±11.95), and IL‐8 (PRE: 53.99±22.56) were increased at POST (IL‐6: 51.41±44.56, IL‐10: 29.55±22.02, IL‐8: 64.99±28.21). POST (vs. PRE) cytokine responses were consistent within each year (p<0.05) and with pooled, 3‐year data (p<0.0001). Although analysis of individual years suggested that PRE markers such as TNF‐α (p<0.019) and IL‐12p70 (p<0.0066) positively correlated with elevated post race gastrointestinal temperatures, analysis of the pooled 3‐year data revealed that PRE cytokine values are not significantly correlated with POST Tgi. Overall, we observed that resting cytokine levels did not identify any chronic inflammation present in subjects who experienced markedly high POST Tgi or exertional heat illness. Ongoing work will elucidate whether post race cytokine values, relative change in individual cytokine responses, or other mechanisms of inflammatory signaling correlate to exertional heat illness incidence and/or abnormally elevated core temperature.Support or Funding InformationFalmouth Road Race, McNair Scholars Program (UConn), CICATS, KSIThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.