Elevation of circulating neutrophil extracellular traps, interleukin (IL)‐8, IL‐22, and vascular endothelial growth factor in patients with venomous snake mamushi (Gloydius blomhoffii) bites

Abstract

Mamushi bites cause swelling and pain that extend from the bitten site. The coagulopathic, anti‐coagulopathic, and vasculopathic actions of mamushi venom result in various laboratory abnormalities, occasionally with muscular, renal, and other organ damage. We investigated the serum biomarkers that were associated with the pathogenesis of mamushi bites, focusing on markers related to tissue‐damage and neutrophil activation. Twenty patients (one case of grade 2, 13 cases of grade 3, and six cases of grade 4 of severity) seen by us in one summer season were enrolled. Peripheral blood samples were taken from the patients on day 0, day 2, and day 7 after mamushi bites. In addition to routine blood examination, serum samples were subjected to enzyme‐linked immunosorbent assay for citrullinated histone H3 (CitH3), interleukin (IL)‐8, IL‐17A, IL‐22, vascular endothelial growth factor (VEGF), high mobility group box protein 1 (HMGB1), tumor necrosis factor (TNF)‐α, and IL‐33. Creatinine kinase (CK) values significantly correlated with prothrombin time (PT) levels, suggesting that muscular damage is associated with exaggerated coagulation and fibrinolysis. In the vast majority of patients, HMGB1, TNF‐α, and IL‐33 were under detection levels. Neutrophil counts did not correlate with PT or CK, indicating that the coagulation disorder and muscular damage were virtually independent of the neutrophil activation. The neutrophil number significantly correlated with CitH3, a representative marker of neutrophil extracellular traps. Moreover, there were significant correlations between neutrophil number, CitH3, IL‐8, IL‐22, and VEGF. Our study suggests that there are two major cascades in mamushi bites. One is an already characterized venom effect on coagulation, vessels, and muscles. In the other novel cascade, we propose that neutrophil activation with IL‐8 leads to the production of IL‐22 and VEGF. This sequential event may contribute to both vascular damage and repair.

DiGeorge syndrome presenting with palmoplantar pustules: Comparative analysis of serum IL‐22, NETs and IL‐8 with usual palmoplantar pustulosis

“…In this study, no significant correlation between CitH3 and neutrophil counts was observed. In our previous study, however, there was a correlation between CitH3 and neutrophil counts in patients with mamushi bites 11 . This suggests that PPP is more focal inflammation than mamushi bites that systemically activate neutrophils.…”

Identification of Risk Areas for Gloydius Snakebites in South Korea

“…Of the more than 3000 known snake species, approximately 200 species (i.e., 15%) are considered dangerous because their bites can be fatal [ 9 , 10 ]. Bites from venomous snakes can cause a wide range of symptoms, from mild symptoms such as respiratory difficulties, headaches, and speech impairment, to severe symptoms including muscle, kidney, and organ damage, potentially leading to death [ 11 , 12 ]. Some venomous snakes tend to ambush from rock crevices, tree roots, or low shrubs, resulting in unexpected snakebite incidents, particularly in mountainous terrain with various landscape features [ 5 , 13 , 14 , 15 ].…”