Serum endothelial monocyte-activating polypeptide-II response after 9 h of passive heat exposure: influence of age, diabetes, or hypertension

Endothelial monocyte-activating polypeptide II (EMAP-II) is a pro-inflammatory cytokine that has been recently shown to be involved in the cellular heat stress response following prolonged work in the heat. However, its response during prolonged passive heat exposure, such as during extreme heat events, or how chronic disease and aging modify this response, is not well characterized. We assessed serum EMAP-II concentrations at baseline and at the end of 9 h of passive heat exposure (end-exposure) (40°C, 9% relative humidity) in 19 young adults (21-27 yr) and 37 older adults (68-73 yr), including subgroups with hypertension (HTN) and/or type 2 diabetes (T2D). EMAP-II concentrations were significantly higher at end-exposure in young adults compared with older adults without HTN or T2D [mean difference (95% confidence interval): 1.9 (0.8, 3.0) pg/mL; <i>P</i> < 0.014], with a greater relative increase from baseline (<i>P</i> = 0.017). EMAP-II concentrations were significantly elevated at baseline in older adults with HTN [4.7 (3.3, 6.1) pg/mL; <i>P</i> < 0.001] and T2D [5.6 (4.2, 7.0) pg/mL; <i>P</i> < 0.001] compared with older adults without HTN or T2D. These elevations persisted at end-exposure in both the older adults with HTN [5.6 (4.2, 7.0) pg/mL; <i>P</i> < 0.001] and/or T2D [5.4 (4.3, 6.4) pg/mL; <i>P</i> < 0.001]. Prolonged passive heat exposure elicited a significant EMAP-II response in young adults. In older adults without HTN or T2D, the response was attenuated, potentially reflecting age-related reductions in cellular stress signaling. In contrast, older adults with HTN and/or T2D showed significant responses, suggesting that chronic disease may heighten inflammatory responses to extreme heat. (ClinicalTrials.gov identifier: NCT04353076)<b>NEW & NOTEWORTHY</b> This study is the first to demonstrate that prolonged passive heat exposure (9 h at 40°C, 9% relative humidity) elicits differential EMAP-II cytokine responses across age and health status. Young adults exhibited significant increases in EMAP-II, whereas older adults without HTN or T2D showed a blunted response. In contrast, older adults with HTN and/or T2D displayed elevated baseline and postexposure EMAP-II, revealing disease-specific inflammatory responses linked to heat vulnerability.