# Role of Serum IL-33 in Bothrops Snakebite Victims: Linking Inflammation and Endothelial Dysfunction

**Authors:** Nicole Coelho Lopes, Ranieri Sales de Souza Santos, Gdayllon Cavalcante Meneses, Leticia Machado de Araújo, Bruna Viana Barroso Martins, Katarina Maria dos Reis Araújo, Marina Coelho Feitosa, Yury Pifano Varela, Fathima Shihana, Sandra Mara Brasileiro Mota, Geraldo Bezerra da Silva Junior, Elizabeth De Francesco Daher, Polianna Lemos Moura Moreira Albuquerque, Alice Maria Costa Martins

PMC · DOI: 10.3390/toxins18020113 · Toxins · 2026-02-23

## TL;DR

This study explores how a protein called IL-33 is linked to bleeding and kidney issues in patients bitten by Bothrops snakes.

## Contribution

The study identifies IL-33 as a novel biomarker associated with bleeding and endothelial dysfunction in Bothrops snakebite victims.

## Key findings

- Elevated IL-33 levels correlate with bleeding and endothelial dysfunction in snakebite patients.
- IL-33 levels are linked to early kidney involvement in Bothrops envenoming.
- IL-33 shows potential as a predictive biomarker for bleeding (AUC = 0.739).

## Abstract

Bothrops snakebites pose a significant public health challenge in low- and middle-income regions, often resulting in inflammation, coagulopathy, and renal complications even after antivenom therapy. This study investigated the role of interleukin-33 (IL-33) and endothelial biomarkers in patients with Bothrops envenoming to better understand the mechanisms associated with bleeding and kidney dysfunction. In a prospective cohort of 31 patients from Northeast Brazil, serum levels of IL-33, von Willebrand factor A2 (vWF-A2), angiopoietin-1, angiopoietin-2, syndecan-1, and VCAM-1 were measured at admission and at 10 and 20 h after antivenom administration. Fourteen patients (45%) presented with bleeding at baseline. Traditional clinical and laboratory parameters did not differ between the bleeding and non-bleeding groups on admission; however, IL-33 levels were significantly higher in patients with bleeding. Elevated IL-33 on admission correlated positively with vWF-A2 and estimated glomerular filtration rate, and negatively with angiopoietin-1, suggesting links between inflammation, endothelial dysfunction, and early renal involvement. IL-33 showed a good performance in bleeding patients (AUC = 0.739; IC 95% 0.562–0.917). These findings identified the link between IL-33, early hemorrhage, endothelial dysfunction, and renal involvement in acute Bothrops envenoming. After antivenom therapy, IL-33 levels presented dynamic changes in all patients and require further studies.

## Linked entities

- **Proteins:** IL33 (interleukin 33), ANGPT2 (angiopoietin 2), sdc1.L (syndecan 1 L homeolog), VCAM1 (vascular cell adhesion molecule 1)
- **Diseases:** coagulopathy (MONDO:0001531)

## Full-text entities

- **Genes:** VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412] {aka CD106, INCAM-100}, Il33 (interleukin 33) [NCBI Gene 77125] {aka 9230117N10Rik, Il-33, Il1f11, NF-HEV}, F2 (coagulation factor II, thrombin) [NCBI Gene 2147] {aka PT, RPRGL2, THPH1}, LCN2 (lipocalin 2) [NCBI Gene 3934] {aka 24p3, MSFI, NGAL, p25}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, SDC1 (syndecan 1) [NCBI Gene 6382] {aka CD138, SDC, SYND1, syndecan}, ANGPT1 (angiopoietin 1) [NCBI Gene 284] {aka AGP1, AGPT, AGPT-1, ANG1, HAE5}, IL33 (interleukin 33) [NCBI Gene 90865] {aka C9orf26, DVS27, IL1F11, NF-HEV, NFEHEV}, HAVCR1 (hepatitis A virus cellular receptor 1) [NCBI Gene 26762] {aka CD365, HAVCR, HAVCR-1, KIM-1, KIM1, TIM}, VWF (von Willebrand factor) [NCBI Gene 7450] {aka F8VWF, VWD}, ANGPT2 (angiopoietin 2) [NCBI Gene 285] {aka AGPT2, ANG2, LMPHM10}
- **Diseases:** Bothrops snakebite (MESH:D012909), renal involvement (MESH:C565423), toxicity (MESH:D064420), vascular injury (MESH:D057772), blood coagulation (MESH:D001778), cardiovascular diseases (MESH:D002318), Bothrops envenoming (MESH:D065008), deaths (MESH:D003643), IRI (MESH:D015427), thrombus (MESH:D013927), haemorrhagic symptoms (MESH:D006474), gingival bleeding (MESH:D005884), tissue injury (MESH:D017695), systemic disorders (MESH:D009422), necrosis (MESH:D009336), PT (MESH:D007020), haemostatic dysfunction (MESH:D006331), kidney damage (MESH:D007674), edema (MESH:D004487), ecchymosis (MESH:D004438), diabetes mellitus (MESH:D003920), Poisoning (MESH:D011041), Endothelial Dysfunction (MESH:D014652), oliguric (MESH:D009846), respiratory diseases (MESH:D012140), hematuria (MESH:D006417), pain (MESH:D010146), renal fibrosis (MESH:D005355), Inflammation (MESH:D007249), injury to (MESH:D014947), anaphylaxis (MESH:D000707), acute or chronic kidney injury (MESH:D058186), Bleeding (MESH:D006470), thromboinflammation (MESH:D000090882), organ dysfunction (MESH:D009102), hematemesis (MESH:D006396)
- **Chemicals:** Cl- (MESH:D002713), Urea (MESH:D014508), Na+ (MESH:D012964), K+ (MESH:D011188), Ca2+ (-), cisplatin (MESH:D002945), calcium (MESH:D002118), Creatinine (MESH:D003404), T3 (MESH:D014284), chloride (MESH:D002712)
- **Species:** Homo sapiens (human, species) [taxon 9606], Bothrops (genus) [taxon 8721], Mus musculus (house mouse, species) [taxon 10090], Serpentes (snakes, infraorder) [taxon 8570]

## Full text

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## References

41 references — full list in the complete paper: https://tomesphere.com/paper/PMC12945279/full.md

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Source: https://tomesphere.com/paper/PMC12945279