Anapirexia e febre em resposta a endotoxina em aves: Desafios metabólicos e mediadores bioquímicos
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Data
2020-09-21
Autores
Amaral Silva, Lara do [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
Apesar das respostas térmicas frente a infecção por patógeno serem decisivas para a sobrevivência das aves, muito ainda há por ser entendido sobre os mecanismos da febre e nada se sabe sobre a queda de temperatura corporal durante a inflamação sistêmica em aves. No presente trabalho desafiamos pintinhos Gallus gallus com altas doses de endotoxina para estudar os mecanismos fisiológicos e bioquímicos da termorregulação de aves frente à inflamação sistêmica. Primeiramente, descrevemos a queda de temperatura corporal durante a inflamação sistêmica em aves como uma resposta regulada (anapirexia). Essa resposta ocorreu por uma inibição de termogênese (redução da taxa metabólica) não relacionada a impedimento da função mitocondrial ou aporte de oxigênio, além de ser apoiada por mecanismos de perda de calor, como ofego e vasodilatação. Em sequência, mostramos que a resposta anapirética à endotoxina parece ser independente da mediação por ciclo-oxigenases (COX), assim o perfil de prostaglandinas (PG) observado neste momento parece não ter função térmica. Também descrevemos que a febre em aves depende da sinalização específica pela COX-2, enzima que quando inibida bloqueia febre via inibição de mecanismos de perda de calor como vasoconstrição e comportamento de agrupamento. Ainda, a febre parece ser majoritariamente dependente da sinalização por PGE2, mas também tem participação das PGD2 e PGF2. No presente trabalho apontamos ainda que a competição com uma demanda energética aumentada por frio, e frio combinado à jejum favorece anapirexia e elimina a resposta de febre nos pintinhos. Finalmente mostramos que a exposição de pintinhos ao poluente dioxina durante o desenvolvimento embrionário resultou em aumento de taxa metabólica (demanda energética). Assim, quando foi induzida a inflamação, os pintinhos apresentaram uma resposta hipometabólica persistente acompanhada da eliminação das respostas hematológicas e osmóticas normais à endotoxina. Concluímos que pintinhos podem responder a um desafio imune tanto com anapirexia como com febre e que a resposta anapirética é favorecida em caso de demandas metabólicas aumentadas. Ainda, a anapirexia não é mediada pela via das COX-PG enquanto a febre é mediada especificamente pela COX-2 e principalmente por PGE2.
Although thermal responses to pathogen infections are decisive for birds’ survival, the mechanisms of fever are largely unknown and no study has addressed the decrease in body temperature during systemic inflammation for birds. Here we challenged Gallus gallus chicks with high doses of endotoxin to study the physiological and biochemical mechanisms of birds’ thermoregulation during systemic inflammation. Firstly, we described the decrease in body temperature during systemic inflammation in birds as a regulated response (anapyrexia). This response was supported by a thermogenesis inhibition (reduced metabolic rate) unrelated to impairment of mitochondrial function or oxygen supply, and also by heat loss mechanisms, such as tachypnea and vasodilation. In sequence, we presented that anapirexia in response to endotoxin was independent of cyclooxygenases mediation (COX), thus the prostaglandin (PG) profile observed during this response did not reflect a thermal function. Moreover, the fever response depended specifically on COX-2 signaling in our chicks, and when it was blocked fever was eliminated by inhibition of heat loss mechanisms such as vasoconstriction and huddling behavior. Yet, fever seems to be mostly dependent on PGE2 signaling, but PGD2 and PGF2 had also a minor increase in expression during fever. Our data also pointed out that competing energetic demands caused by cold, and cold combined with fasting favors anapyrexia and eliminates the fever response in chicks. Finally, we show that the exposure of chicks to the pollutant dioxin during embryonic development resulted in increased in metabolic rate. Thus, when inflammation was induced, these chicks showed a persistent hypometabolic response accompanied by the elimination of normal hematological and osmotic responses to endotoxin. We conclude that chicks can respond to an immune challenge with both anapyrexia and fever, and the anapyretic response is favored in case of increased metabolic demands. Furthermore, anapyrexia is not mediated by the COX-PG pathway, whereas fever is mediated specifically by COX-2 and mainly by PGE2.
Although thermal responses to pathogen infections are decisive for birds’ survival, the mechanisms of fever are largely unknown and no study has addressed the decrease in body temperature during systemic inflammation for birds. Here we challenged Gallus gallus chicks with high doses of endotoxin to study the physiological and biochemical mechanisms of birds’ thermoregulation during systemic inflammation. Firstly, we described the decrease in body temperature during systemic inflammation in birds as a regulated response (anapyrexia). This response was supported by a thermogenesis inhibition (reduced metabolic rate) unrelated to impairment of mitochondrial function or oxygen supply, and also by heat loss mechanisms, such as tachypnea and vasodilation. In sequence, we presented that anapirexia in response to endotoxin was independent of cyclooxygenases mediation (COX), thus the prostaglandin (PG) profile observed during this response did not reflect a thermal function. Moreover, the fever response depended specifically on COX-2 signaling in our chicks, and when it was blocked fever was eliminated by inhibition of heat loss mechanisms such as vasoconstriction and huddling behavior. Yet, fever seems to be mostly dependent on PGE2 signaling, but PGD2 and PGF2 had also a minor increase in expression during fever. Our data also pointed out that competing energetic demands caused by cold, and cold combined with fasting favors anapyrexia and eliminates the fever response in chicks. Finally, we show that the exposure of chicks to the pollutant dioxin during embryonic development resulted in increased in metabolic rate. Thus, when inflammation was induced, these chicks showed a persistent hypometabolic response accompanied by the elimination of normal hematological and osmotic responses to endotoxin. We conclude that chicks can respond to an immune challenge with both anapyrexia and fever, and the anapyretic response is favored in case of increased metabolic demands. Furthermore, anapyrexia is not mediated by the COX-PG pathway, whereas fever is mediated specifically by COX-2 and mainly by PGE2.
Descrição
Palavras-chave
Anapirexia, Ciclo-oxigenase, Desafios metabólicos, Febre, Pintinhos, Prostaglandinas, Anapyrexia, Cyclooxygenases, Metabolic challenges, Fever, Chicks, Prostaglandins