10 research outputs found
Characterization of the Thermoregulatory Response to Pituitary Adenylate Cyclase-Activating Polypeptide in Rodents
Knocking out the transient receptor potential vanilloid-1 (TRPV1) gene promotes the development of age-related obesity in mice: an insight into mechanisms.
Forest plot analysis of mortality rate using random-effects model in septic patients with hypothermia (body temperature up to 36.0°C; <i>n</i> = 890).
<p>Forest plot analysis of mortality rate using random-effects model in septic patients with hypothermia (body temperature up to 36.0°C; <i>n</i> = 890).</p
Forest plot analysis of mortality rate using random-effects model in septic patients with fever (body temperature above 38.0°C; <i>n</i> = 6,040).
<p>Forest plot analysis of mortality rate using random-effects model in septic patients with fever (body temperature above 38.0°C; <i>n</i> = 6,040).</p
Forest plot analysis of mortality rate using random-effects model in septic patients with normothermia (body temperature between 36.1 and 38.0°C; <i>n</i> = 3,904).
<p>Forest plot analysis of mortality rate using random-effects model in septic patients with normothermia (body temperature between 36.1 and 38.0°C; <i>n</i> = 3,904).</p
Flowchart of study selection and inclusion.
<p>Flowchart of study selection and inclusion.</p
Meta-regression analysis of the association between body temperature and mortality ratio in septic patients (<i>n</i> = 10, 834).
<p>Meta-regression analysis of the association between body temperature and mortality ratio in septic patients (<i>n</i> = 10, 834).</p
The Neurokinin-1 Receptor Contributes to the Early Phase of Lipopolysaccharide-Induced Fever via Stimulation of Peripheral Cyclooxygenase-2 Protein Expression in Mice
Neurokinin (NK) signaling is involved in various inflammatory processes. A common manifestation of systemic inflammation is fever, which is usually induced in animal models with the administration of bacterial lipopolysaccharide (LPS). A role for the NK1 receptor was shown in LPS-induced fever, but the underlying mechanisms of how the NK1 receptor contributes to febrile response, especially in the early phase, have remained unknown. We administered LPS (120 µg/kg, intraperitoneally) to mice with the Tacr1 gene, i.e., the gene encoding the NK1 receptor, either present (Tacr1+/+) or absent (Tacr1−/−) and measured their thermoregulatory responses, serum cytokine levels, tissue cyclooxygenase-2 (COX-2) expression, and prostaglandin (PG) E2 concentration. We found that the LPS-induced febrile response was attenuated in Tacr1−/− compared to their Tacr1+/+ littermates starting from 40 min postinfusion. The febrigenic effect of intracerebroventricularly administered PGE2 was not suppressed in the Tacr1−/− mice. Serum concentration of pyrogenic cytokines did not differ between Tacr1−/− and Tacr1+/+ at 40 min post-LPS infusion. Administration of LPS resulted in amplification of COX-2 mRNA expression in the lungs, liver, and brain of the mice, which was statistically indistinguishable between the genotypes. In contrast, the LPS-induced augmentation of COX-2 protein expression was attenuated in the lungs and tended to be suppressed in the liver of Tacr1−/− mice compared with Tacr1+/+ mice. The Tacr1+/+ mice responded to LPS with a significant surge of PGE2 production in the lungs, whereas Tacr1−/− mice did not. In conclusion, the NK1 receptor is necessary for normal fever genesis. Our results suggest that the NK1 receptor contributes to the early phase of LPS-induced fever by enhancing COX-2 protein expression in the periphery. These findings advance the understanding of the crosstalk between NK signaling and the “cytokine-COX-2-prostaglandin E2” axis in systemic inflammation, thereby open up the possibilities for new therapeutic approaches