Distinct inflammatory markers in primary and secondary dengue infection: can cytokines CXCL5, CXCL9, and CCL17 act as surrogate markers?

ABSTRACT

Dengue fever poses a significant global health threat, with symptoms including dengue hemorrhagic fever and dengue shock syndrome. Each year, India experiences fatal dengue outbreaks with severe manifestations. The primary cause of severe inflammatory responses in dengue is a cytokine storm. Individuals with a secondary dengue infection of a different serotype face an increased risk of complications due to antibody-dependent enhancement. Therefore, it is crucial to identify potential risk factors and biomarkers for effective disease management. In the current study, we assessed the prevalence of dengue infection in and around Aligarh, India, and explored the role of cytokines, including CXCL5, CXCL9, and CCL17, in primary and secondary dengue infections, correlating them with various clinical indices. Among 1,500 suspected cases, 367 tested positive for dengue using Real-Time PCR and ELISA. In secondary dengue infections, the serum levels of CXCL5, CXCL9, and CCL17 were significantly higher than in primary infections (P < 0.05). Dengue virus (DENV)-2 showed the highest concentrations of CXCL5 and CCL17, whereas DENV-1 showed the highest concentrations of CXCL9. Early detection of these cytokines could serve as potential biomarkers for diagnosing severe dengue, and downregulation of these cytokines may prove beneficial for the treatment of severe dengue infections.

KEYWORDS:

• Dengue
• Real-Time PCR
• serotypes
• cytokine
• CXCL5
• CXCL9
• CCL17

List of abbreviations

DENV	=	Dengue virus
DENV-1	=	Dengue virus serotype-1
DENV-2	=	Dengue virus serotype-2
DENV-3	=	Dengue virus serotype-3
DENV-4	=	Dengue virus serotype-4
ELISA	=	Enzyme-linked immunosorbent assay
AUC	=	Area under curve
K-S test	=	Kolmogorov–Smirnov test
AMU	=	Aligarh Muslim University
DHR	=	Department of Health Research
ICMR	=	Indian Council of Medical Research

Acknowledgments

Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2024R39), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article.

Institutional review board statement

Ethical approval was obtained from the Institutional Ethics Committee of the Faculty of Medicine, AMU, Aligarh, India

Informed consent statement

Written informed consent was obtained from all patients and their caregivers.

Additional information

Funding

All research work was conducted in the Viral Research and Diagnostic Laboratory (funded by ICMR/DHR), Department of Microbiology, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.