Abstract
Snakebites are considered a major public health problem worldwide. In the Amazon region of Brazil, the snake Bothrops atrox (B. atrox) is responsible for 90% of the bites. These bites may cause local and systemic signs from acute inflammatory reaction and hemostatic changes, and present common hemorrhagic disorders. These alterations occur due the action of hemostatically active and immunogenic toxins which are capable of triggering a wide range of hemostatic and inflammatory events. However, the crosstalk between coagulation disorders and inflammatory reaction still has gaps in snakebites. Thus, the goal of this study was to describe the relationship between the consumption of fibrinogen and the profile of inflammatory molecules (chemokines and cytokines) in evenomations by B. atrox snakebites. A prospective study was carried out with individuals who had suffered B. atrox snakebites and presented different levels of fibrinogen consumption (normal fibrinogen [NF] and hypofibrinogenemia [HF]). Seventeen patients with NF and 55 patients with HF were eligible for the study, in addition to 50 healthy controls (CG). The molecules CXCL-8, CCL-5, CXCL-9, CCL-2, CXCL-10, IL-6, TNF, IL-2, IL-10, IFN-γ, IL-4, and IL-17A were quantified in plasma using the CBA technique at three different times (pre-antivenom therapy [T0], 24 h [T1], and 48 h [T2] after antivenom therapy). The profile of the circulating inflammatory response is different between the groups studied, with HF patients having higher concentrations of CCL-5 and lower IFN-γ. In addition, antivenom therapy seems to have a positive effect, leading to a profile of circulating inflammatory response similar in quantification of T1 and T2 on both groups. Furthermore, these results suggest that a number of interactions of CXCL-8, CXCL-9, CCL-2, IL-6, and IFN-γ in HF patients are directly affected by fibrinogen levels, which may be related to the inflammatory response and coagulation mutual relationship induced by B. atrox venom. The present study is the first report on inflammation-coagulation crosstalk involving snakebite patients and supports the better understanding of envenomation's pathophysiology mechanisms and guides in the search for novel biomarkers and prospective therapies.
Highlights
Snakebite is a neglected tropical disease and a major public health problem in developing countries worldwide
We observed a significant increase in CXCL-8, CCL-5, CXCL-9, CCL-2, CXCL-10, and IL-6 among the groups exposed to the venom (NF and HF), previously to antivenom therapy (T0), when compared to the control group (CG)
Our results suggest that number of interactions of CXCL-8, CXCL-9, CCL-2, IL-6, and IFN-γ in HF patients are directly affected by fibrinogen levels, which may be related to the inflammatory response and coagulation mutual relationship induced by B. atrox venom (Figure 6)
Summary
Snakebite is a neglected tropical disease and a major public health problem in developing countries worldwide It is an important cause of morbidity and mortality, especially in areas of extreme poverty in the tropics and subtropics, such as subSaharan Africa, South, and Southeast Asia, Papua New Guinea, Central and Latin America [1]. Clinical manifestations observed in victims of Bothrops snakebites are characterized by varied local and systemic effects, as a result of the action of biologically active toxins in the venom [2, 8]. Among these effects, inflammatory and hemostatic disorders are frequently observed in patients. Envenomation’s by viperid snakes often cause local and systemic bleeding [9, 10], such as gingivorrhagia, epistaxis, hematemesis, hematuria, bleeding in the uteris, and placenta (in pregnant women) [11, 12] and bleeding in the central nervous system [13,14,15,16]
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