Central serotonin prevents hypotension and hypothermia and reduces plasma and spleen cytokine levels during systemic inflammation.
Brain Behav Immun
; 80: 255-265, 2019 08.
Article
em En
| MEDLINE
| ID: mdl-30885841
ABSTRACT
An exceptionally high mortality rate is observed in sepsis and septic shock. Systemic administration of lipopolysaccharide (LPS) has been used as an experimental model for sepsis resulting in an exacerbated immune response, brain neurochemistry adjustments, hypotension, and hypothermia followed by fever. Central serotonergic pathways not only modulate systemic inflammation (SI) but also are affected by SI, including in the anteroventral region of the hypothalamus (AVPO), which is the hierarchically most important region for body temperature (Tb) control. In this study, we sought to determine if central serotonin (5-HT) plays a role in SI induced by intravenous administration of LPS (1.5â¯mg/kg) in male Wistar rats (280-350â¯g) by assessing 5-HT levels in the AVPO, mean arterial pressure, heart rate, and Tb up to 300â¯min after LPS administration, as well as assessing plasma and spleen cytokine levels, nitric oxide (NO) plasma levels, and prostaglandin (PG) E2 levels in the AVPO at 75â¯min and 300â¯min after LPS administration. We observed reduced AVPO 5-HT levels, hypotension, tachycardia, hypothermia followed by fever, as well as observing increased plasma NO, plasma and spleen cytokines and AVPO PGE2 levels in SI. Intracerebroventricular (icv) administration of 5-HT 30â¯min before LPS administration prevented hypotension and hypothermia, which were accompanied by reduced plasma NO, as well as plasma TNF-α, IL-1ß, IL-6, and IL-10 and spleen TNF-α and IL-10 levels. We suggest that SI reduced 5-HT levels in the AVPO favor an increased pro-inflammatory status both centrally and peripherally that converge to hypotension and hypothermia. Moreover, our results are consistent with the notion that exogenous 5-HT given icv prevents hypotension and hypothermia probably activating the splenic anti-inflammatory pathway.
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Base de dados:
MEDLINE
Assunto principal:
Baço
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Serotonina
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Citocinas
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Hipotensão
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Hipotermia
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Inflamação
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article