Lower levels of CXCL-8 and IL-2 on admission as predictors of early adverse reactions to Bothrops antivenom in the Brazilian Amazon

Abstract

Snakebite envenomings are considered a global health problem. The specific therapy for these envenomings consists of administering animal-derived antivenoms aiming to neutralize the venom toxins. Antivenoms have been used effectively to treat snakebites for more than a century; however, their administration may result in early and/or late adverse reactions. The present study presents the prevalence of early adverse reactions (EARs) towards Bothrops antivenom therapy in a health tertiary unit in the Brazilian Amazon and explores if specific plasma cytokines and chemokines from envenomed patients could be used as predictors of EARs. A cohort of patients bitten by Bothrops atrox was followed-up at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD), from 2014 to 2016. Patients were treated with the Brazilian Bothrops antivenom and CXCL-8, CCL-5, CXCL-9, CCL-2, CXCL-10, IL-6, TNF, IL-2, IL-10, IFN-y, IL-4, and IL-17A were evaluated in patients' plasma samples before and after antivenom administration. From the total of patients (n = 186), mostly were male (82.3%), inhabiting rural areas (87.1%), with an average age of 35 years. Most of the patients (83.8%) were admitted to the hospital within 6 h after the accident, 26 (14%) reported having suffered a previous snakebite, and 97 (52.1%) received between 7 and 9 antivenom vials. The frequency of antivenom-induced EARs was 11.8% (22), resulting mostly of mild reactions. Urticaria was the major EAR manifestation (46.4%). Interestingly, CXCL-8 and IL-2 showed significantly lower levels in patients who progressed to EARs, although IL-2 levels might not represent biological relevance due the small magnitude difference between groups. This study reveals that CXCL-8 and IL-2 could play a role in the onset of EARs in pit viper envenomings.

Keywords: Adverse reaction; Antivenom; Bothrops; CXCL-8; Chemokine; Cytokine; Hypersensitivity; IL-2; Snakebite.