Endothelial injury and acute-phase inflammatory mediators converge to drive dengue severity

Endothelial injury and acute-phase inflammatory mediators converge to drive dengue severity | medRxiv Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Endothelial injury and acute-phase inflammatory mediators converge to drive dengue severity Abdul R. Anshad , Muthuvel Atchaya , Shanmugam Saravanan , Amudhan Murugesan , Pachamuthu Balakrishnan , Sivadoss Raju , Yong K. Yong , View ORCID Profile Marie Larsson , View ORCID Profile Esaki M. Shankar doi: https://doi.org/10.64898/2026.03.18.26348673 Abdul R. Anshad 1 Infection and Inflammation, Department of Biotechnology, Central University of Tamil Nadu , Neelakudi, Thiruvarur 610 005, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Muthuvel Atchaya 1 Infection and Inflammation, Department of Biotechnology, Central University of Tamil Nadu , Neelakudi, Thiruvarur 610 005, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Shanmugam Saravanan 2 Department of Microbiology, Saveetha Medical College and Hospital, Saveetha University , Chennai 602 105, India 3 Infectious Diseases Research Collaboratives, Global Research Cell, Dr. D. Y. Patil Vidyapeeth University , Pune, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Amudhan Murugesan 4 Deparment of Microbiology, The Government Theni Medical College and Hospital , Theni, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Pachamuthu Balakrishnan 5 Department of Research, Meenakshi Academy of Higher Education and Research , Chennai 600 078, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Sivadoss Raju 6 State Public Health Laboratory, Directorate of Public Health and Preventive Medicine , Chennai, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site Yong K. Yong 7 Laboratory Center, Xiamen University Malaysia , Sepang, Malaysia Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marie Larsson 8 Molecular Medicine and Virology, Department of Biomedical and Clinical Sciences, Linköping University , Linköping 58 185, Sweden Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Marie Larsson For correspondence: shankarem{at}cutn.ac.in marie.larsson{at}liu.se Esaki M. Shankar 1 Infection and Inflammation, Department of Biotechnology, Central University of Tamil Nadu , Neelakudi, Thiruvarur 610 005, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Esaki M. Shankar For correspondence: shankarem{at}cutn.ac.in marie.larsson{at}liu.se Abstract Full Text Info/History Metrics Data/Code Preview PDF Abstract Introduction Severe dengue infection is characterized by endothelial injury and systemic inflammatory complications. To better understand the mechanisms underlying disease severity, we investigated a broad panel of circulating inflammatory and endothelial mediators in patients with clinical dengue infection. Methods A prospective cross-sectional case–control study was carried out involving 111 dengue patients and 42 healthy controls. Among the dengue cases, 85 were identified as primary, while 26 were classified as secondary dengue infections. Serum levels of endothelial markers (Ang-2, CXCL10, MCP1, TRAIL), acute-phase and liver dysfunction and acute-phase markers (CRP, galectin 3, and serum amyloid protein), systemic inflammatory mediators (MIF, TNF-α, IL-1β), mast cell-derived proteases (chymase, tryptase), and tissue repair markers HGF, IL-10, IL-1Ra) were quantified using ELISA and Luminex multiplex assays. Correlations among serum analytes, severity indicators, and haematological markers were also explored Results Several biomarkers, Ang-2, CXCL10, TRAIL, CRP, MIF, IL-1Ra, TNF-α, and chymase showed differential expression across severity groups, indicating coordinated endothelial and inflammatory activation. Stratification of patients with primary-secondary dengue also followed a similar pattern except IL-1β, which had significant differential expression across the cohorts. Ang-2 showed strong positive correlations with markers of hepatic dysfunction, including ALT, AST, and bilirubin, suggesting a link between endothelial injury and liver involvement. Conclusions Severe dengue is driven by the coordinated activation of endothelial dysfunction, acute-phase responses, mast cell mediators, and counter-regulatory pathways. These processes collectively contribute to vascular leakage and organ injury, reinforcing the value of biomarkers such as Ang-2, CXCL10, CRP, and chymase for severity assessment. Competing Interest Statement The authors have declared no competing interest. Funding Statement A.R.A is funded by NFOBC-NBCFDC of the Ministry of Social Justice, Government of India, as Senior Research Fellowship. The authors also acknowledge funding support received from M.L. through 2021-02703, the Swedish Research Council ( https://www.vr.se/english.html ), The Joanna Cocozza Foundation for Children's Medical Research, and Linkoping University Hospital Research, CALF. The funders of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the report. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of SMCH, Chennai (Ref. No. 114/03/2024/Faculty/SRB/SMCH) and TMC, Theni (Ref. No. 2300/IEC/2024-26) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present work are contained in the manuscript. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license . Back to top Previous Next Posted March 19, 2026. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. You are going to email the following Endothelial injury and acute-phase inflammatory mediators converge to drive dengue severity Message Subject (Your Name) has forwarded a page to you from medRxiv Message Body (Your Name) thought you would like to see this page from the medRxiv website. Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Share Endothelial injury and acute-phase inflammatory mediators converge to drive dengue severity Abdul R. Anshad , Muthuvel Atchaya , Shanmugam Saravanan , Amudhan Murugesan , Pachamuthu Balakrishnan , Sivadoss Raju , Yong K. Yong , Marie Larsson , Esaki M. Shankar medRxiv 2026.03.18.26348673; doi: https://doi.org/10.64898/2026.03.18.26348673 Share This Article: Copy Citation Tools Endothelial injury and acute-phase inflammatory mediators converge to drive dengue severity Abdul R. Anshad , Muthuvel Atchaya , Shanmugam Saravanan , Amudhan Murugesan , Pachamuthu Balakrishnan , Sivadoss Raju , Yong K. Yong , Marie Larsson , Esaki M. 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