title: IL-8 Alterations in HIV-1 Infected Children With Disease Progression.
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.
authors.affiliation: From 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).
authors.forename: Ambili Nair
authors.initials: AN
authors.lastname: Pananghat
authors.forename: Heena
authors.initials: H
authors.lastname: Aggarwal
authors.forename: Somi Sankaran
authors.initials: SS
authors.lastname: Prakash
authors.forename: Muzamil Ashraf
authors.initials: MA
authors.lastname: Makhdoomi
authors.forename: Ravinder
authors.initials: R
authors.lastname: Singh
authors.forename: Rakesh
authors.initials: R
authors.lastname: Lodha
authors.forename: Shakir
authors.initials: S
authors.lastname: Ali
authors.forename: Maddur
authors.initials: M
authors.lastname: Srinivas
authors.forename: Bimal Kumar
authors.initials: BK
authors.lastname: Das
authors.forename: Ravindra Mohan
authors.initials: RM
authors.lastname: Pandey
authors.forename: Sushil Kumar
authors.initials: SK
authors.lastname: Kabra
authors.forename: Kalpana
authors.initials: K
authors.lastname: Luthra
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D004270:DNA, Circular; D018450:Disease Progression; D005260:Female; D051380:GRB2 Adaptor Protein / Q000276:immunology; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007223:Infant; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D007963:Leukocytes, Mononuclear; D008297:Male; D012333:RNA, Messenger; D060888:Real-Time Polymerase Chain Reaction; D023062:Receptors, Interleukin-8A / Q000096:biosynthesis / Q000276:immunology; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; C508606:CXCL8 protein, human; D004270:DNA, Circular; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D016209:Interleukin-8; D012333:RNA, Messenger; D023062:Receptors, Interleukin-8A; C579041:GAPDHS protein, human; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)