{"doi":"10.1111/bph.70000","title":"Spontaneous and pharmacologically induced hypothermia protect mice against endotoxic shock","abstract":"BACKGROUND AND PURPOSE: Despite the well-known occurrence of hypothermia during sepsis, its underlying biological nature and adaptive value remain debated. EXPERIMENTAL APPROACH: 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). KEY RESULTS: 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. CONCLUSION AND IMPLICATIONS: Collectively, our findings indicate that spontaneous and pharmacologically-induced hypothermia protect against endotoxic shock.","journal":"British Journal of Pharmacology","year":2025,"id":517112,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1236452,"name":"Warda Merchant","orcid":null,"position":1,"is_corresponding":false},{"id":1382976,"name":"Alam Khan","orcid":"0000-0002-2482-7403","position":2,"is_corresponding":false},{"id":526298,"name":"Surbhi","orcid":null,"position":3,"is_corresponding":false},{"id":385221,"name":"Alexandre Caron","orcid":"0000-0001-6939-6136","position":4,"is_corresponding":false},{"id":457339,"name":"Ryan Reynolds","orcid":"0000-0002-3781-0766","position":5,"is_corresponding":false},{"id":366036,"name":"Lin Jia","orcid":"0000-0002-7653-7395","position":6,"is_corresponding":false},{"id":257962,"name":"Laurent Gautron","orcid":"0000-0003-3609-7441","position":7,"is_corresponding":false},{"id":1148722,"name":"Arely Tinajero","orcid":null,"position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-19T02:48:54.768083Z","pmid":"39987925","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}