Immunomodulation of the inflammatory response induced by Androctonus australis hector neurotoxins: biomarker interactions.

OBJECTIVE

Androctonus australis hector (Aah) is the most dangerous scorpion in the Maghreb countries. Its venom contains three major neurotoxins (Aah I, Aah II and Aah III), which are responsible for almost all the lethal effects caused in mammals. These toxins act on the voltage-gated sodium channels of excitable cells. The targets and the lethal effects of these toxins have been extensively studied. However, their effects on the induced immune response after envenoming have not deeply elicited. We therefore investigated the effects induced by Aah venom and its toxic components, mainly its main toxin Aah II, on the activation of the inflammatory process.

METHODS

Wistar rats were injected by intraperitoneal route with a sublethal dose of Aah venom, FTox-G50, the purified Aah II toxin or with 400 μl of sterile physiological saline solution. Immunological biomarkers such as MPO, NO and ICAM-1 were analyzed in serum in lung tissue. Cytokine levels were also determined in serum at 3, 6 and 24 h after envenoming.

RESULTS

We report in this study that intraperitoneal injection of the venom or its toxins (the whole toxic fraction or Aah II toxin) caused an inflammatory reaction involving increased neutrophil release into blood and neutrophil accumulation in lung tissue. This cell infiltration was associated with the release of NO, histamine, cytokines (IL-1, IL-6, IL-12, IL-4 and IL-5) and ICAM.

CONCLUSION

Aah II binding to its targets, in this case Na⁺ channels, may induce a cascade of events such as inflammatory mediator release and neutrophil migration that could contribute to the exacerbation of the systemic inflammatory response and the development of lung injury following scorpion envenoming.