Fluoxetine mitigates hypothermia and inflammatory responses in lipopolysaccharide-induced systemic inflammation: Insights into serotonergic and hypothalamic thermoregulatory mechanisms

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-03-08 DOI:10.1016/j.cyto.2025.156909

Isis P. Trajano , Luis Henrique Angenendt Costa , Patrícia Passaglia , Wanderson S. Santos , Jonathas Rodrigo dos Santos , Luciane Carla Alberici , Luiz G.S. Branco

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引用次数: 0

Abstract

An abnormally elevated mortality rate is evident in cases of sepsis. To study specific mechanisms of sepsis experimentally, lipopolysaccharide (LPS) systemically administered has been used as a model, in which an exaggerated immune response, neurochemistry settings, and fever following hypothermia take place. Notably, systemic inflammation (SI) can modulate the central serotonergic pathways and being influenced by it. This influence extends to the hypothalamus, which holds a hierarchical significance in the control of body temperature (Tb). This study investigates the potential impact of orally administered fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI) given orally for 7 days before on LPS-induced SI (1.5 mg/kg, i.v.) in rats. The assessment involved monitoring Tb, heat loss index (HLI), along non-shivering thermogenesis assessed by oxygen consumption. Cytokine levels in the spleen and blood, along with nitric oxide (NO), and prostaglandins (PGs) E₂ and D_2, levels were also measured. The findings reveal increased plasma NO, cytokines in plasma and spleen, and hypothalamus PGE₂ levels during SI. Interestingly, FLX mitigated LPS-induced hypothermia, accompanied by a reduction in plasma and splenic NO, interleukins (IL) 6, and 10. Additionally, the results align with the hypothesis that hypothermia, blunted by FLX, develops in fact in a regulated form, as an adaptive strategy.

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.