关键词: IL-1β IL-6 IL1R1 IL1R2 IL6R IL6ST LPS TNFRSF1A TNFRSF1B TNFα brain

Mesh : Administration, Intravenous Animals Caffeine / administration & dosage pharmacology Choroid Plexus / drug effects immunology Cytokines / genetics Disease Models, Animal Encephalitis / chemically induced drug therapy genetics Female Gene Expression Regulation / drug effects Hypothalamus / drug effects immunology Interleukin-1beta / genetics Interleukin-6 / metabolism Lipopolysaccharides / adverse effects Sheep Tumor Necrosis Factor-alpha / genetics

来  源:   DOI:10.3390/ijms222413237

Abstract:
This study was designed to determine the effect of acute caffeine (CAF) administration, which exerts a broad spectrum of anti-inflammatory activity, on the synthesis of pro-inflammatory cytokines and their receptors in the hypothalamus and choroid plexus (ChP) during acute inflammation caused by the injection of bacterial endotoxin-lipopolysaccharide (LPS). The experiment was performed on 24 female sheep randomly divided into four groups: control; LPS treated (iv.; 400 ng/kg of body mass (bm.)); CAF treated (iv.; 30 mg/kg of bm.); and LPS and CAF treated. The animals were euthanized 3 h after the treatment. It was found that acute administration of CAF suppressed the synthesis of interleukin (IL-1β) and tumor necrosis factor (TNF)α, but did not influence IL-6, in the hypothalamus during LPS-induced inflammation. The injection of CAF reduced the LPS-induced expression of TNF mRNA in the ChP. CAF lowered the gene expression of IL-6 cytokine family signal transducer (IL6ST) and TNF receptor superfamily member 1A (TNFRSF1) in the hypothalamus and IL-1 type II receptor (IL1R2) in the ChP. Our study on the sheep model suggests that CAF may attenuate the inflammatory response at the hypothalamic level and partly influence the inflammatory signal generated by the ChP cells. This suggests the potential of CAF to suppress neuroinflammatory processes induced by peripheral immune/inflammatory challenges.
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