Interleukin-1 receptor-induced PGE(2) production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation

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Reis, Mouzarllem B. ^{[1, 2, 3]} ; Rodrigues, Fernanda L. ^{[4, 5]} ; Lautherbach, Natalia ^{[6, 4]} ; Kanashiro, Alexandre ^[7] ; Sorgi, Carlos A. ^{[8, 1]} ; Meirelles, Alyne F. G. ^[1] ; Silva, Carlos A. A. ^[4] ; Zoccal, Karina F. ^[9] ; Souza, Camila O. S. ^{[1, 2]} ; Ramos, Simone G. ^[10] ; Matsuno, Alessandra K. ^[11] ; Rocha, Lenaldo B. ^[12] ; Salgado, Helio C. ^[4] ; Navegantes, Luiz C. C. ^[4] ; Kettelhut, Isis C. ^[4] ; Cupo, Palmira ^[11] ; Gardinassi, Luiz G. ^{[13, 1, 2]} ; Faccioli, Lucia H. ^{[1, 2]}

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^[1] Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, Sao Paulo - Brazil

^[2] Fac Med Ribeirao Preto, Programa Posgrad Imunol Basica & Aplicada, Sao Paulo - Brazil

^[3] Ctr Univ Barao Maua Ribeirao Preto, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Fisiol, Sao Paulo - Brazil

^[5] Univ Fed Mato Grosso do Sul, Fac Med, Campus Tres Lagoas CPTL, Mato Grosso - Brazil

^[6] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, Sao Paulo - Brazil

^[7] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Neurociencias & Ciencias Comportamento, Sao Paulo - Brazil

^[8] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, Sao Paulo - Brazil

^[9] Ctr Univ Barao Maua, Ribeirao Preto, SP - Brazil

^[10] Fac Med Ribeirao Preto, Dept Patol & Med Legal, Sao Paulo - Brazil

^[11] Fac Med Ribeirao Preto, Dept Puericultura & Pediat, Sao Paulo - Brazil

^[12] Univ Fed Triangulo Mineiro, Inst Ciencias Biol & Nat, Uberaba, MG - Brazil

^[13] Univ Fed Goias, Inst Patol Trop & Saude Publ, Goiania, Go - Brazil

• Tipo de documento: Artigo Científico
• Fonte: NATURE COMMUNICATIONS; v. 11, n. 1 OCT 28 2020.
• Citações Web of Science: 2

Resumo

Scorpion envenomation is a leading cause of morbidity and mortality among accidents caused by venomous animals. Major clinical manifestations that precede death after scorpion envenomation include heart failure and pulmonary edema. Here, we demonstrate that cardiac dysfunction and fatal outcomes caused by lethal scorpion envenomation in mice are mediated by a neuro-immune interaction linking IL-1 receptor signaling, prostaglandin E-2,E- and acetylcholine release. IL-1R deficiency, the treatment with a high dose of dexamethasone or blockage of parasympathetic signaling using atropine or vagotomy, abolished heart failure and mortality of envenomed mice. Therefore, we propose the use of dexamethasone administration very early after envenomation, even before antiserum, to inhibit the production of inflammatory mediators and acetylcholine release, and to reduce the risk of death. Cardiac dysfunction is a major complication that precedes death after scorpion envenomation. Here, authors show that heart failure and mortality are caused by excessive acetylcholine release, which requires IL-1R-dependent PGE2 production. Dexamethasone treatment effectively inhibits cardiac dysfunction and mortality. (AU)

• Processo FAPESP: 15/21976-1 - Controle autonômico cardiovascular em camundongos knockout para receptores toll-like 9 com hipertensão induzida por angiotensina II.
• Beneficiário: Fernanda Luciano Rodrigues
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/07125-6 - Novos aspectos funcionais dos eicosanóides
• Beneficiário: Lúcia Helena Faccioli
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 17/02314-3 - Investigação sobre alterações cardíacas que ocorrem no envenenamento pela peçonha do escorpião Tityus serrulatus
• Beneficiário: Mouzarllem Barros dos Reis
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/00658-1 - Novos aspectos funcionais dos eicosanóides
• Beneficiário: Lúcia Helena Faccioli
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários