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

ABSTRACT: 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 E2, 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.

SUBMITTER: Reis MB

PROVIDER: S-EPMC7595177 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Interleukin-1 receptor-induced PGE<sub>2</sub> production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation.

Reis Mouzarllem B MB Rodrigues Fernanda L FL Lautherbach Natalia N Kanashiro Alexandre A Sorgi Carlos A CA Meirelles Alyne F G AFG Silva Carlos A A CAA Zoccal Karina F KF Souza Camila O S COS Ramos Simone G SG Matsuno Alessandra K AK Rocha Lenaldo B LB Salgado Helio C HC Navegantes Luiz C C LCC Kettelhut Ísis C ÍC Cupo Palmira P Gardinassi Luiz G LG Faccioli Lúcia H LH

Nature communications 20201028 1

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<sub>2,</sub> and acetylcholine release. IL-1R deficiency, the tr ...[more]

PMID: 33116136

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Project description:BackgroundHigh circulating interleukin (IL)-18 level predicts a higher hospitalization rate among dialysis patients, possibly through cardiovascular mechanisms; however, whether higher IL-18 level is associated with mortality in dialysis patients is less clear. In addition, its impacts on left ventricular (LV) function are also unknown. We conducted a cohort study to examine the impacts of IL-18 level on LV function and prognosis among clinically stable hemodialysis patients.MethodsClinically stable patients undergoing maintenance hemodialysis (? 3 months) were prospectively enrolled from December 2008 to January 2009, and were followed up for 31 months. The enrolled patients (41% male, 66.4 ± 10.9 years of age) received 2-dimensional echocardiography and myocardial deformation (strain) analysis, including LV peak systolic longitudinal strain (GLS) and circumferential strain (CS). Laboratory measurements were also performed. Cox regression analysis was used to investigate prognostic factors.ResultsSeventy-five patients were stratified into 2 groups by the median value of IL-18 (654.2 pg/ml). Between these 2 groups, there was no significant difference in baseline characteristics including LV ejection fraction. The high IL-18 group had a worse LV systolic function as demonstrated by reduced GLS and CS. Seventeen patients (22.7%) died during the follow-up period. Multivariate Cox regression analysis showed that low serum albumin, the presence of hypertension, high serum IL-18, and less negative GLS (>-15%) were independently associated with all-cause mortality. No significant interaction between IL-18 and less negative GLS was noted in the final Cox model.ConclusionHemodialysis patients with high IL-18 levels tend to have worse LV systolic function and higher mortality rate. However, elevated serum IL-18 level is predictive of poor prognosis among stable hemodialysis patients, independently of LV dysfunction. This suggests an additional value of IL-18 to echocardiographic study in predicting all-cause mortality, and IL-18 may be helpful in early risk stratification of hemodialysis patients.

Dataset Information

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

Publications

Interleukin-1 receptor-induced PGE<sub>2</sub> production controls acetylcholine-mediated cardiac dysfunction and mortality during scorpion envenomation.

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