Acta physiologica (Oxford, England) · 2019
Increased hypothalamic hydrogen sulphide contributes to endotoxin tolerance by down-modulating PGE2 production.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Santos Bruna M, Francescato Heloísa D C, Turcato Flávia C, Antunes-Rodrigues José, Coimbra Terezila M, Branco Luiz G S
Аннотация
AIM: Whereas some patients have important changes in body core temperature (Tb) during systemic inflammation, others maintain a normal Tb, which is intrinsically associated to immune paralysis. One classical model to study immune paralysis is the use of repeated administration of lipopolysaccharide (LPS), the so-called endotoxin tolerance. However, the neuroimmune mechanisms of endotoxin tolerance remain poorly understood. Hydrogen sulphide (H2 S) is a gaseous neuromodulator produced in the brain by the enzyme cystathionine β-synthase (CBS). The present study assessed whether endotoxin tolerance is modulated by hypothalamic H2 S.
METHODS: Rats with central cannulas (drug microinjection) and intraperitoneal datalogger (temperature record) received a low-dose of lipopolysaccharide (LPS; 100 µg kg-1 ) daily for four consecutive days. Hypothalamic CBS expression and H2 S production rate were assessed, together with febrigenic signalling. Tolerant rats received an inhibitor of H2 S synthesis (AOA, 100 pmol 1 µL-1 icv) or its vehicle in the last day.
RESULTS: Antero-ventral preoptic area of the hypothalamus (AVPO) H2 S production rate and CBS expression were increased in endotoxin-tolerant rats. Additionally, hypothalamic H2 S inhibition reversed endotoxin tolerance reestablishing fever, AVPO and plasma PGE2 levels without altering the absent plasma cytokines surges.
CONCLUSION: Endotoxin tolerance is not simply a reflection of peripheral reduced cytokines release but actually results from a complex set of mechanisms acting at multiple levels. Hypothalamic H2 S production modulates most of these mechanisms.
METHODS: Rats with central cannulas (drug microinjection) and intraperitoneal datalogger (temperature record) received a low-dose of lipopolysaccharide (LPS; 100 µg kg-1 ) daily for four consecutive days. Hypothalamic CBS expression and H2 S production rate were assessed, together with febrigenic signalling. Tolerant rats received an inhibitor of H2 S synthesis (AOA, 100 pmol 1 µL-1 icv) or its vehicle in the last day.
RESULTS: Antero-ventral preoptic area of the hypothalamus (AVPO) H2 S production rate and CBS expression were increased in endotoxin-tolerant rats. Additionally, hypothalamic H2 S inhibition reversed endotoxin tolerance reestablishing fever, AVPO and plasma PGE2 levels without altering the absent plasma cytokines surges.
CONCLUSION: Endotoxin tolerance is not simply a reflection of peripheral reduced cytokines release but actually results from a complex set of mechanisms acting at multiple levels. Hypothalamic H2 S production modulates most of these mechanisms.