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Updated: Mar 20, 2026
In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
IL-8 Alterations in HIV-1 Infected Children With Disease Progression
Ambili Nair Pananghat1, Heena Aggarwal, Somi Sankaran Prakash
1From the Department of Biochemistry (ANP, HA, SSP, MAM, KL), Department of Pediatrics (RS, RL, SKK), Department of Microbiology (BKD), Department of Pediatrics Surgery (MS), Department of Biostatistics (RMP), All India Institute of Medical Sciences (RMP), and Department of Biochemistry, Jamia Hamdard University, New Delhi, India (ANP, SA).
Insights
Interleukin-8 (IL-8) is elevated in children with faster HIV-1 disease progression, correlating negatively with CD4 counts. Antiretroviral therapy (ART) reduces IL-8 levels, suggesting its potential as a prognostic marker.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- HIV-1 infection progresses faster in children than adults.
- Long-term nonprogressors (LTNPs) are rare (<5%) and maintain stable CD4 counts.
- Understanding host immune responses in different disease stages is crucial for managing pediatric HIV-1.
Purpose of the Study:
- To investigate the role of interleukin-8 (IL-8) in HIV-1 immunopathogenesis in children.
- To assess IL-8 as a potential prognostic marker for disease progression and ART efficacy.
Main Methods:
- Analyzed T- and B-cell activation gene expression in 14 HIV-1 infected children (ART-naïve and treated) and 8 controls.
- Quantified IL-8, CXCR1, and SHP2 mRNA expression via qRT-PCR.
- Measured plasma IL-8 levels using flow cytometry.
Main Results:
- Higher IL-8 expression was observed in ART-naïve progressors and ART nonresponders compared to LTNPs and ART responders.
- IL-8, CXCR1, and SHP2 mRNA levels were significantly higher in progressors versus LTNPs.
- Plasma IL-8 levels correlated negatively with CD4 counts in ART-naïve subjects and positively with viral load in ART-treated children.
Conclusions:
- IL-8 may serve as a prognostic marker for HIV-1 disease progression in children, alongside CD4 counts.
- ART initiation led to a significant reduction in IL-8 mRNA and plasma levels, indicating ART's anti-inflammatory effect.
- IL-8 monitoring could help assess ART efficacy in pediatric HIV-1 management.
Abstract:
Disease progression in HIV-1 infected children is faster than in adults. Less than 5% of the infected children maintain stable CD4 counts beyond 7 years of infection and are termed long-term nonprogressors (LTNPs). Delineating the host immune response in antiretroviral naïve (ART) and treated HIV-1 infected children at different disease stages will help in understanding the immunopathogenesis of the disease.A total of 79 asymptomatic, perinatally HIV-1 infected children (50 ART naïve and 29 ART treated) and 8 seronegative donors were recruited in this study. T- and B-cell activation PCR arrays were performed from the cDNA, using total RNA extracted from the peripheral blood mononuclear cells (PBMCs) of 14 HIV-1 infected children at different stages of the disease. The differentially expressed genes were identified. Quantitative RT-PCR was performed for the (interleukin-8) IL-8 gene and its transcriptional mediators, that is, SHP2, GRB2, and IL-8R (IL-8 receptor/CXCR1). Plasma levels of IL-8 were measured by flow cytometry.Gene array data revealed a higher expression of IL-8 in the ART naïve HIV-1 infected progressors and in ART nonresponders than LTNPs and ART responders, respectively. Quantitative RT-PCR analysis demonstrated a significant higher expression of IL-8 (P < 0.001), its receptor CXCR1 (P = 0.03) and the upstream signaling molecule SHP2 (P = 0.04) in the progressors versus LTNPs. Plasma levels of IL-8 were significantly higher in progressors versus LTNPs (P < 0.001), and ART nonresponders versus ART responders (P < 0.001). A significant negative correlation of plasma levels of IL-8 with CD4 counts (cells/μL) was observed in HIV-1 infected ART naïve subjects (r = -0.488; P < 0.001), while the IL-8 levels positively correlated with viral load in the ART treated children (r = 0.5494; P < 0.001). ART naïve progressors on follow up demonstrated a significant reduction in the mRNA expression (P = 0.05) and plasma levels of IL-8 (P = 0.05) post 6 months of ART initiation suggesting the beneficial role of ART therapy in reducing inflammation in infected children.Our data suggest that IL-8 may serve as a potential prognostic marker in adjunct with CD4 counts to monitor disease progression in the HIV-1 infected children and the efficacy of ART.
