Interleukin-1 receptor-induced PGE2 production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation

• Published in: Nature communications Vol. 11; no. 1; p. 5433
• Main Authors: Reis, Mouzarllem B., Rodrigues, Fernanda L., Lautherbach, Natalia, Kanashiro, Alexandre, Sorgi, Carlos A., Meirelles, Alyne F. G., Silva, Carlos A. A., Zoccal, Karina F., Souza, Camila O. S., Ramos, Simone G., Matsuno, Alessandra K., Rocha, Lenaldo B., Salgado, Helio C., Navegantes, Luiz C. C., Kettelhut, Ísis C., Cupo, Palmira, Gardinassi, Luiz G., Faccioli, Lúcia H.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.10.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13/21; 13/31; 38; 38/77; 49/1; 631/250/256/2516; 631/250/371; 64/60; 692/4019/592; Acetylcholine; Atropine; Congestive heart failure; Death; Dexamethasone; Edema; Heart failure; Humanities and Social Sciences; Inflammation; Interleukin 1; Interleukin 1 receptors; Morbidity; Mortality; multidisciplinary; Parasympathetic nervous system; Prostaglandin E2; Receptors; Risk reduction; Science; Science (multidisciplinary); Signaling; Vagotomy; Venom
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-19232-8

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, 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.