CCL-2 and CXCL-8: Potential Prognostic Biomarkers of Acute Kidney Injury after a Bothrops atrox Snakebite

Abstract

In the Brazilian Amazon, the snake Bothrops atrox is the primary cause of snakebites. B. atrox (BaV) venom can cause systemic pathophysiological changes such as acute kidney injury (AKI), which leads to the production of chemokines and cytokines in response to the envenomation. These soluble immunological molecules act by modulating the inflammatory response; however, the mechanisms associated with the development of AKI are still poorly understood. Here, we characterize the profile of these soluble immunological molecules as possible predictive biomarkers of the development of AKI. The study involved 34 patients who had been victims of snakebites by Bothrops sp. These were categorized into two groups according to the development of AKI (AKI(-)/AKI(+)), using healthy donors as the control (HD). Peripheral blood samples were collected at three-time points: before antivenom administration (T0) and at 24 and 48 hours after antivenom (T1 and T2, respectively). The soluble immunological 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 using cytometric bead array. Our results demonstrated an increase in CXCL-9, CXCL-10, IL-6, IL-2, IL-10, and IL-17A molecules in the groups of patients who suffered Bothrops snakebites (AKI(-) and AKI(+)) before antivenom administration, when compared to HD. In the AKI(+) group, levels of CXCL-8 and CCL-2 molecules were elevated on admission and progressively decreased during the clinical evolution of patients after antivenom administration. In addition, in the signature analysis, these were produced exclusively by the group AKI(+) at T0. Thus, these chemokines may be related to the initiation and extension of AKI after envenomation by Bothrops and present themselves as two potential biomarkers of AKI at T0.

The role of CXCL family members in different diseases

“…Many authors showed that the activation of renal vascular endothelium promoted the production of immunological CXC chemokine molecules. Take CXCL8 for a example, it was proved to recruit the neutrophils, assisting the activation of inflammatory pathways in the ischemic kidney and culminating the acute kidney injury [ 88 ]. As another proinflammatory gene, CXCL5 also makes the similar effect on renal inflammation and impairment of kidney function as CXCL8 [ 89 ].…”

Bothrops venom-induced hemostasis disorders in the rat: Between Scylla and Charybdis

“…This excessive inflammatory response may have clinical consequences. Increased MCP-1 level was associated with a AKI in B. atrox envenomation in the Brazilian Amazon [88]. However, more studies are needed to identify inflammatory biomarkers predictive of the prothrombotic risk in the time-course of Bothrops envenomation, even after antivenom administration.…”

Exploring the Profile of Cell Populations and Soluble Immunological Mediators in Bothrops atrox Envenomations

“…The cytokine IL-10 is characterized as a key molecule in the regulation of the immune response, which is capable of suppressing the activation of neutrophils and monocytes, and, consequently, the production of chemokines and cytokines, thus regulating the inflammatory processes and cytotoxic pathways [ 53 , 54 ]. Our data from the integrative analysis of the immunological molecules demonstrated the effective participation of IL-10, with several interactions established before and after the administration of antivenom in the MILD group compared with the SEV group, which may be related to the lower severity in these patients ( Figure 3 ).…”