Immune response to snake envenoming and treatment with antivenom; complement activation, cytokine production and mast cell degranulation.
BACKGROUND
Snake bite is one of the most neglected public health issues in poor rural communities worldwide. In addition to the clinical effects of envenoming, treatment with antivenom frequently causes serious adverse reactions, including hypersensitivity reactions (including anaphylaxis) and pyrogenic reactions. We aimed to investigate the immune responses to Sri Lankan snake envenoming (predominantly by Russell's viper) and antivenom treatment.


RESULTS
Plasma concentrations of Interleukin (IL)-6, IL-10, tumor necrosis factor α (TNFα), soluble TNF receptor I (sTNFRI), anaphylatoxins (C3a, C4a, C5a; markers of complement activation), mast cell tryptase (MCT), and histamine were measured in 120 Sri Lankan snakebite victims, both before and after treatment with antivenom. Immune mediator concentrations were correlated with envenoming features and the severity of antivenom-induced reactions including anaphylaxis. Envenoming was associated with complement activation and increased cytokine concentrations prior to antivenom administration, which correlated with non-specific systemic symptoms of envenoming but not with coagulopathy or neurotoxicity. Typical hypersensitivity reactions to antivenom occurred in 77/120 patients (64%), satisfying criteria for a diagnosis of anaphylaxis in 57/120 (48%). Pyrogenic reactions were observed in 32/120 patients (27%). All patients had further elevations in cytokine concentrations, but not complement activation, after the administration of antivenom, whether a reaction was noted to occur or not. Patients with anaphylaxis had significantly elevated concentrations of MCT and histamine.


CONCLUSIONS
We have demonstrated that Sri Lankan snake envenoming is characterized by significant complement activation and release of inflammatory mediators. Antivenom treatment further enhances the release of inflammatory mediators in all patients, with anaphylactic reactions characterised by high levels of mast cell degranulation but not further complement activation. Anaphylaxis is probably triggered by non allergen-specific activation of mast cells and may be related to the quality of available antivenom preparations, as well as a priming effect from the immune response to the venom itself.
Centre for Clinical Research in Emergency Medicine, Western Australian Institute for Medical Research and the University of Western Australia, Perth, Western Australia, Australia. Shelley.Stone@uwa.edu.au
Shelley F
SF
Stone
Geoffrey K
GK
Isbister
Seyed
S
Shahmy
Fahim
F
Mohamed
Chandana
C
Abeysinghe
Harendra
H
Karunathilake
Ariaranee
A
Ariaratnam
Tamara E
TE
Jacoby-Alner
Claire L
CL
Cotterell
Simon G A
SG
Brown
D000328:Adult; D000707:Anaphylaxis / Q000139:chemically induced; D000818:Animals; D000997:Antivenins / Q000009:adverse effects / Q000627:therapeutic use*; D003167:Complement Activation; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000276:immunology*; D008875:Middle Aged; D012909:Snake Bites / Q000276:immunology* / Q000628:therapy*; D013188:Sri Lanka
D000997:Antivenins; D016207:Cytokines; D018836:Inflammation Mediators