Snake envenoming causes rapid systemic and local effects that often result in fatal or long-term disability outcomes. It seems likely that acute phase and inflammatory responses contribute to these haemorrhagic, coagulopathic, neurotoxic, nephrotoxic and local tissue destructive pathologies. However, the contributory role of acute phase/inflammatory responses to envenoming is under-researched and poorly understood-particularly for envenoming by sub-Saharan African venomous snakes. To provide data to help guide future studies of human patients, and to explore the rationale for adjunct anti-inflammatory medication, here we used an in vivo murine model to systematically assess acute phase and inflammatory responses of mice to ten African
snake venoms. In addition to investigating snake species-specific effects of
venom on the cardiovascular system and other key organs and tissues, we examined the response to intravascular envenoming by
acute phase reactants, including
serum amyloid A,
P-selectin and
haptoglobin, and several
cytokines.
Venoms of the spitting (Naja nigricollis) and forest (N. melanoleuca) cobras resulted in higher acute phase and inflammatory responses than
venoms from the other cobras, mambas and vipers tested. Naja nigricollis
venom also stimulated a 100-fold increase in systemic
interleukin 6. Thin blood films from
venom-treated mice revealed species-specific changes in red blood cell morphology, indicative of membrane abnormalities and functional damage,
lymphopenia and neutrophil
leukocytosis. Our ex vivo assays with healthy human blood treated with these
venoms identified that N. nigricollis
venom induced marked levels of
haemolysis and platelet aggregation. We conclude that African
snake venoms stimulate very diverse responses in this mouse model of acute systemic envenoming, and that
venoms of the African cobras N. nigricollis and N. melanoleuca, in particular, cause marked inflammatory and non-specific
acute phase responses. We also report that several African
snake venoms cause haemolytic changes. These findings emphasise the importance of understanding acute responses to envenoming, and that further research in this area may facilitate new diagnostic and treatment approaches, which in turn may lead to better clinical outcomes for
snakebite patients.