IL-8 Alterations in HIV-1 Infected Children With Disease Progression. Issue 21 (May 2016)

• Record Type: Journal Article
• Authors: Pananghat, Ambili Nair; Aggarwal, Heena; Prakash, Somi Sankaran; Makhdoomi, Muzamil Ashraf; Singh, Ravinder; Lodha, Rakesh; Ali, Shakir; Srinivas, Maddur; Das, Bimal Kumar; Pandey, Ravindra Mohan; Kabra, Sushil Kumar; Luthra, Kalpana
• Editors: Leeansyah., Edwin
• Is Part Of: Medicine. Volume 95:Issue 21(2016)
• Page Start: e3734
• Publication Date: 2016-05
• Subjects: Medicine -- Periodicals; Medicine -- Periodicals; Médecine -- Périodiques; Geneeskunde; Medicine; Periodicals; Periodicals; 610.5
• DOI: 10.1097/MD.0000000000003734
• Languages: English
• ISSNs: 0025-7974

Abstract

Abstract : Supplemental Digital Content is available in the text Abstract : 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.