The influence of environmental and core temperature on cyclooxygenase and PGE2 in healthy humans

Abstract

Whether cyclooxygenase (COX)/prostaglandin E2 (PGE2) thermoregulatory pathways, observed in rodents, present in humans? Participants (n = 9) were exposed to three environments; cold (20 °C), thermoneutral (30 °C) and hot (40 °C) for 120 min. Core (Tc)/skin temperature and thermal perception were recorded every 15 min, with COX/PGE2 concentrations determined at baseline, 60 and 120 min. Linear mixed models identified differences between and within subjects/conditions. Random coefficient models determined relationships between Tc and COX/PGE2. Tc [mean (range)] increased in hot [+ 0.8 (0.4–1.2) °C; p < 0.0001; effect size (ES): 2.9], decreased in cold [− 0.5 (− 0.8 to − 0.2) °C; p < 0.0001; ES 2.6] and was unchanged in thermoneutral [+ 0.1 (− 0.2 to 0.4) °C; p = 0.3502]. A relationship between COX2/PGE2 in cold (p = 0.0012) and cold/thermoneutral [collapsed, condition and time (p = 0.0243)] was seen, with higher PGE2 associated with higher Tc. A within condition relationship between Tc/PGE2 was observed in thermoneutral (p = 0.0202) and cold/thermoneutral [collapsed, condition and time (p = 0.0079)] but not cold (p = 0.0631). The data suggests a thermogenic response of the COX/PGE2 pathway insufficient to defend Tc in cold. Further human in vivo research which manipulates COX/PGE2 bioavailability and participant acclimation/acclimatization are warranted to elucidate the influence of COX/PGE2 on Tc.

Effect of chronic deltamethrin exposure on brain transcriptome and metabolome of juvenile crucian carp

“…One unexpected finding was that Del exposure upregulates cox2 expression while suppressing the production of PGG2. We speculated that the unstable prostaglandin intermediary PGG2 is highly unstable in the brain and then rapidly transformed into PGH2 via specific enzymatic activities 40 . Overall, our results suggested that the metabolic pathway for arachidonic acid was dysregulated after chronic Del exposure.…”

Molecular biomarkers for assessing the heat-adapted phenotype: a narrative scoping review

“…Orexin serves a number of functions, including regulating sleep and wake states, feeding behaviour, reward systems, mood and cognition [ 24 ], with evidence from animal studies indicating that orexin is also implicated in the regulation of body temperature at rest [ 134 , 223 ] and during exercise [ 123 ]. However, whilst the findings of Shin et al [ 198 ] are promising, it has been noted that this study did not adjust for the plasma volume changes occurring with HA and should therefore be interpreted cautiously [ 43 ]. Moreover, they are based on a limited sample size ( n = 9), and an atypical HA regime consisting of 10 bouts of 30-min hot water immersion over a 3-week period, as well as deep and mean body temperature calculation from tympanic measurement which is of questionable validity (e.g.…”

“…Although the role of energy homeostasis in thermoregulation is well accepted [ 200 ], it has mainly been studied within the context of exposure to cold, and in the control of the production of additional heat via the influence of hypothalamic-pituitary-thyroid axis on the metabolic processes that constitute facultative (non-shivering) thermogenesis [ 195 ]. Similarly, the role of the prostaglandin–cyclooxygenase system is well established in febrile temperature regulation [ 86 ] and has recently received some attention in the context of exposure to cold [ 43 , 50 ]. However, there is some evidence suggesting that these processes may also play a role in the adaptive processes to chronic heat exposure and as such may be suitable for further investigation in the context identifying a biomarker of the head adapted phenotype.…”

“…Although the role of this pathway in non-febrile temperature regulation is less well established, COX-2 gene deficient mice are unable to effectively defend their deep body temperature during cold exposure [ 116 ]. Research in humans has shown a thermogenic response of the COX-2/PGE 2 pathways during acute (120 min) cold exposure in humans and a relationship between rectal temperature and PGE 2 during acute exposure to cold and thermoneutral conditions, although no effects were evident during acute exposure to hot (40 °C; 40% R.H.) conditions [ 43 ]. Similarly, administration of acetaminophen, a COX enzyme inhibitor, reduced core temperature of humans during an acute (120 min) passive exposure to 20 °C, 40% R.H [ 51 ] as well as during running [ 19 ] and cycling [ 126 ] exercise in the heat (30 °C, 50% R.H.); this latter finding has been challenged [ 28 ], whilst studies that have used forearm dermal microdialysis of COX inhibitors indicate that both COX isoforms may be involved in sudomotor regulation in the heat [ 58 ], although in contrast to studies of oral COX inhibitors (which may influence central and peripheral thermoregulatory mechanisms), microdialysis administration will only exert peripheral effects.…”