Bothrops lanceolatus snake (Fer-de-lance) venom triggers inflammatory mediators’ storm in human blood

Systemic increased inflammatory mediators’ levels are a hallmark in a plethora of pathological conditions, including thrombotic diseases as the envenomation by Bothrops lanceolatus snake. Multiple organ infarctions, which are not prevented by anticoagulant therapy, are the main cause of death on this envenomation. However, the potential mechanisms involved in these systemic reactions are underexplored. This study aimed to explore the potential systemic events which could contribute to thrombotic reactions on the envenomation by B. lanceolatus in an ex vivo human whole-blood model. B. lanceolatus venom elicited an inflammatory reaction, which was characterized by a strong complement activation, since we detected high C3a, C4a and C5a anaphylatoxins levels. Besides, the venom promoted soluble Terminal Complement Complex (sTCC) assembly. Complement activation was accompanied by intense lipid mediators’ release, which included LTB4, PGE2 and TXB2. In addition, in the blood exposed to B. lanceolatus venom, we detected IL-1β, IL-6 and TNF-α interleukins production. Chemokines, including CCL2, CCL5 and CXCL8 were upregulated in the venom presence. These outcomes show that B. lanceolatus venom causes a strong inflammatory reaction in the blood favoring a potential setting to thrombi formation. Thus, inhibiting inflammatory mediators or their receptors may help in the envenomed patients’ management.
Keywords
Bothrops lanceolatus venom;  Systemic inflammation;  Complement activation;  Lipid mediators;  Interleukins;  Chemokines

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França FS, Gabrili JJM, Mathieu L, Burgher F, Blomet J, Tambourgi DV. Bothrops lanceolatus snake (Fer-de-lance) venom triggers inflammatory mediators’ storm in human blood. Arch. Toxicol.. 2021 ;in press. doi:10.1007/s00204-020-02959-0.
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