Is prostaglandin E2 (PGE2) involved in the thermogenic response to environmental cooling in healthy humans?

Foster, Josh; Mauger, Alexis R.; Chrismas, Bryna C. R.; Thomasson, Katie; Taylor, Lee

doi:10.1016/j.mehy.2015.07.022

Cited by 14 publications

(10 citation statements)

References 58 publications

(94 reference statements)

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“…Moreover, it is unclear if APAP induced hypothermia is exacerbated in cold conditions (where there is a greater reliance on thermogenesis), which may be inhibited in the presence of a COX inhibitor (such as APAP). This specific hypothesis has recently been proposed by our group ( Foster et al, 2015 ), and should be investigated in future work. These findings could have implications for public health recommendations.…”

Section: Discussionmentioning

confidence: 56%

“…When administered orally (1000 mg), APAP is a potent inhibitor of COX-2 in intact cells, but may also inhibit COX-1 ( Hinz et al, 2008 ). Given that participants in this study were exposed to sub-neutral environmental temperatures, it is possible that COX may have been prevented from activating thermogenic responses to this environment ( Foster et al, 2015 ). Although the role of COX in non-febrile thermogenesis remains a topic of debate ( Aronoff and Romanovsky, 2007 ; Foster et al, 2015 ), recent evidence supports a role for COX in this capacity.…”

Section: Discussionmentioning

confidence: 99%

“…Despite its well-established validity as an analgesic and antipyretic via inhibition of cyclooxygenase (COX; Aronoff et al, 2006 ; Li et al, 2008 ), a growing body of evidence also demonstrates a third, hypothermic action of APAP, namely core temperature (T C ) reduction in the absence of fever. This side effect may be beneficial for inducing therapeutic hypothermia, but may also increase rates of accidental hypothermia (via exacerbated T C reductions in environments beneath thermal neutrality; Foster et al, 2015 ). 4°C reductions in T C have been shown within rodents following intravenous APAP administration ( Li et al, 2008 ; Ayoub et al, 2011 ; Gentry et al, 2015 ).…”

Section: Introductionmentioning

confidence: 99%

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Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans

et al. 2016

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In non-febrile mouse models, high dose acetaminophen administration causes profound hypothermia. However, this potentially hazardous side-effect has not been confirmed in non-febrile humans. Thus, we sought to ascertain whether an acute therapeutic dose (20 mg⋅kg lean body mass) of acetaminophen would reduce non-febrile human core temperature in a sub-neutral environment. Ten apparently healthy (normal core temperature, no musculoskeletal injury, no evidence of acute illness) Caucasian males participated in a preliminary study (Study 1) to determine plasma acetaminophen concentration following oral ingestion of 20 mg⋅kg lean body mass acetaminophen. Plasma samples (every 20 min up to 2-hours post ingestion) were analyzed via enzyme linked immunosorbent assay. Thirteen (eight recruited from Study 1) apparently healthy Caucasian males participated in Study 2, and were passively exposed to 20°C, 40% r.h. for 120 min on two occasions in a randomized, repeated measures, crossover design. In a double blind manner, participants ingested acetaminophen (20 mg⋅kg lean body mass) or a placebo (dextrose) immediately prior to entering the environmental chamber. Rectal temperature, skin temperature, heart rate, and thermal sensation were monitored continuously and recorded every 10 min. In Study 1, the peak concentration of acetaminophen (14 ± 4 μg/ml) in plasma arose between 80 and 100 min following oral ingestion. In Study 2, acetaminophen ingestion reduced the core temperature of all participants, whereas there was no significant change in core temperature over time in the placebo trial. Mean core temperature was significantly lower in the acetaminophen trial compared with that of a placebo (p < 0.05). The peak reduction in core temperature in the acetaminophen trial was reached at 120 min in six of the thirteen participants, and ranged from 0.1 to 0.39°C (average peak reduction from baseline = 0.19 ± 0.09°C). There was no significant difference in skin temperature, heart rate, or thermal sensation between the acetaminophen and placebo trials (p > 0.05). The results indicate oral acetaminophen reduces core temperature of humans exposed to an environment beneath the thermal neutral zone. These results suggest that acetaminophen may inhibit the thermogenic mechanisms required to regulate core temperature during exposure to sub-neutral environments.

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of Acetaminophen Ingestion on Thermoregulation of Normothermic, Non-febrile Humans

et al. 2016

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“…Despite this data, additional criteria, such as the environmental temperature, are needed to accurately predict when acetaminophen poses the greatest risk for hypothermia development. Since the COX pathway could be involved in non-febrile thermogenesis [14,15], inhibition of this enzyme by acetaminophen might cause Tc to fall during cold exposure, while exerting negligible effects on Tc while exposed to a warm environment.…”

Section: Introductionmentioning

confidence: 99%

“…The aim of this trial was to examine the thermoregulatory response to acetaminophen administration (20 mg/kg of lean body mass) during a 120-minute exposure to a thermo-neutral and cold environment in healthy adult humans. Due to a potential role of COX in non-febrile thermogenesis [14,15], it was hypothesised that acetaminophen would reduce Tc in cold conditions, but have no effect on Tc in thermo-neutral conditions relative to a placebo.…”

Section: Introductionmentioning

confidence: 99%