The Baylor College of Medicine Pediatric HIV Research Center intends to pursue the inter-relationships of sleep, fatigue and HIV/AIDS (RFA-HL-04-010) in older children and adolescents infected with HIV-1. The Center will do so by exploring the molecular relationships between HIV-1 infection and homeostatic sleep-regulating cytokines, and hormones soluble tumor necrosis factor alpha receptor I (sTNF-alpha RI) and interleukin-6 (IL-6), growth hormone-releasing hormone (GHRH), and corticotropin-releasing hormone (CRH). This will be accomplished by repeat (12-month repeat) 24-hr studies of HIV-1 infected subjects and control subjects admitted to the General Clinical Research Center (GCRC) at Texas Children's Hospital. The hypothesis for this research project is that HIV-1 infection upregulates the secretion of sTNF-alpha RI, IL-6, GHRH, and CRH, producing a state of fatigue, sleepiness, and insomnia that, itself, forms an inflammatory immune response and spread of HIV-disease progression (as compared to a cytotoxic immune response that contains HIV-infection) and contributes to a decline in neurocognitive ability. Among the studies that will be used to validate this hypothesis are: 1) validated sleep questionnaires and actigraphy; 2) peripheral blood measurements of sTNF-alpha RI, IL-6, GHRH, CRH, cortisol, lymphocytes, absolute and CD4+ T-cell counts, interferon-gamma (IFN-gamma), interleukin-1 receptor antagonist (IL-1 RA), IL-10, IL-12, HIV-1 RNA; and 3) neurocognitive assessments. Based upon preliminary observations, it is expected that there will be significant correlations between HIV-1 viral burden, and elevations in sTNF-alpha RI, IL-6, GHRH, and CRH. Also, TH1 cytotoxic cytokines (IFN-gamma, IL-12) would be expected to be lowered and anti-inflammatory cytokines (IL-10, IL-1RA) to be elevated. HIV-1 infected older children and adolescents with more progressive HIV-1 disease would be expected to have more documented sleep disorders and lower neurocognitive scores. This significance of these studies is that they will attempt to define the molecular connections between the neuroendocrine sleep-regulating cytokines and hormones (TNF-alpha RI, IL-6, GHRH, CRH) and the immune response, in particular, the shifting away from a cytotoxic response (IFN-gamma, IL-12). In addition, neurocognitive correlates will be made in patients with sleep disturbance and fatigue. Thus, these studies may help explain the effects of HIV-1 infection upon the sleep regulating pathways of the neuroendocrine-immune pathways that accelerate HIV-1 disease progression and contribute to the loss of neurocognitive function and general debilitation of children infected with HIV-1 perinatally or through risky adult-type behavior.
| Shearer, William T; Corry, David B (2012) High prevalence of asthma in HIV-infected adults: new insights. J Allergy Clin Immunol 129:715-6 |
| Foster, Samuel B; Lu, Ming; Glaze, Daniel G et al. (2012) Associations of cytokines, sleep patterns, and neurocognitive function in youth with HIV infection. Clin Immunol 144:13-23 |
| Foster, Samuel B; Lu, Ming; Thompson, Bruce et al. (2010) Association between HLA inheritance and asthma medication use in HIV positive children. AIDS 24:2133-5 |
| Chinen, Javier; Shearer, William T (2010) Advances in basic and clinical immunology in 2009. J Allergy Clin Immunol 125:563-8 |
| Chinen, Javier; Shearer, William T (2009) Advances in basic and clinical immunology in 2008. J Allergy Clin Immunol 123:328-32 |
| Lipshultz, Steven E; Wilkinson, James D; Messiah, Sarah E et al. (2009) Clinical research directions in pediatric cardiology. Curr Opin Pediatr 21:585-93 |
| Shearer, William T; Notarangelo, Luigi D; Griffith, Linda M (2008) Treatment of immunodeficiency: long-term outcome and quality of life. J Allergy Clin Immunol 122:1065-8 |
| Chinen, Javier; Shearer, William T (2008) Advances in basic and clinical immunology in 2007. J Allergy Clin Immunol 122:36-41 |
| Shearer, William T (2008) Breastfeeding and HIV infection. Pediatrics 121:1046-7 |
| Foster, Samuel B; McIntosh, Kenneth; Thompson, Bruce et al. (2008) Increased incidence of asthma in HIV-infected children treated with highly active antiretroviral therapy in the National Institutes of Health Women and Infants Transmission Study. J Allergy Clin Immunol 122:159-65 |
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