{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tinajero A"],"funding":["NIDDK NIH HHS","National Institute of Diabetes and Digestive and Kidney Diseases","National Institutes of Health","Initiative of The University of Texas System","NIH HHS"],"pagination":["2621-2641"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12092199"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["182(12)"],"pubmed_abstract":["<h4>Background and purpose</h4>Despite the well-known occurrence of hypothermia during sepsis, its underlying biological nature and adaptive value remain debated.<h4>Experimental approach</h4>Using indirect calorimetry, telemetry, thermal gradient studies and pharmacological studies, we examined the thermal and metabolic responses of mice treated with a shock-inducing lethal dose of lipopolysaccharide (LPS).<h4>Key results</h4>We report that LPS-treated mice undergo spontaneous hypothermia, driven by hypometabolism and cold-seeking behaviours, even when animals approach the end of life. Conversely, rewarming LPS-treated mice at 30°C delayed hypothermia but worsened mortality, thus highlighting the adaptive importance of hypothermia. Additionally, we show that LPS-induced hypothermia was partly mediated by peripheral neurotensin expressed in response to vascular toll-like receptor 4 (TLR4) signalling. The administration of a neurotensin analogue (JMV449) induced pharmacological hypothermia and significantly ameliorated the clinical presentation and lethality rates in LPS-treated mice. Moreover, the therapeutic benefits of pharmacological hypothermia were prevented when LPS-treated mice were switched to 30°C. Lastly, these beneficial outcomes were attributed to a reduction in oxygen consumption, metabolic stress and cytopathic hypoxia, rather than the modulation of the cytokine storm.<h4>Conclusion and implications</h4>Collectively, our findings indicate that spontaneous and pharmacologically-induced hypothermia protect against endotoxic shock."],"journal":["British journal of pharmacology"],"pubmed_title":["Spontaneous and pharmacologically induced hypothermia protect mice against endotoxic shock."],"pmcid":["PMC12092199"],"funding_grant_id":["S10 OD021684","1S10OD021684-01","1S10OD021684‐01","P01 DK119130","P30 DK127984","TRC4","P01DK119130","P30DK127984"],"pubmed_authors":["Caron A","Gautron L","Merchant W","Khan A","Reynolds R","Surbhi","Jia L","Tinajero A"],"additional_accession":[]},"is_claimable":false,"name":"Spontaneous and pharmacologically induced hypothermia protect mice against endotoxic shock.","description":"<h4>Background and purpose</h4>Despite the well-known occurrence of hypothermia during sepsis, its underlying biological nature and adaptive value remain debated.<h4>Experimental approach</h4>Using indirect calorimetry, telemetry, thermal gradient studies and pharmacological studies, we examined the thermal and metabolic responses of mice treated with a shock-inducing lethal dose of lipopolysaccharide (LPS).<h4>Key results</h4>We report that LPS-treated mice undergo spontaneous hypothermia, driven by hypometabolism and cold-seeking behaviours, even when animals approach the end of life. Conversely, rewarming LPS-treated mice at 30°C delayed hypothermia but worsened mortality, thus highlighting the adaptive importance of hypothermia. Additionally, we show that LPS-induced hypothermia was partly mediated by peripheral neurotensin expressed in response to vascular toll-like receptor 4 (TLR4) signalling. The administration of a neurotensin analogue (JMV449) induced pharmacological hypothermia and significantly ameliorated the clinical presentation and lethality rates in LPS-treated mice. Moreover, the therapeutic benefits of pharmacological hypothermia were prevented when LPS-treated mice were switched to 30°C. Lastly, these beneficial outcomes were attributed to a reduction in oxygen consumption, metabolic stress and cytopathic hypoxia, rather than the modulation of the cytokine storm.<h4>Conclusion and implications</h4>Collectively, our findings indicate that spontaneous and pharmacologically-induced hypothermia protect against endotoxic shock.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jun","modification":"2026-04-26T03:21:09.392Z","creation":"2026-04-26T03:09:50.695Z"},"accession":"S-EPMC12092199","cross_references":{"pubmed":["39987925"],"doi":["10.1111/bph.70000"]}}