RESUMO
BACKGROUND: Interleukin-10 (IL-10) is a potent immunoregulatory cytokine. IL-10-promoter polymorphisms have been shown to affect human immunodeficiency virus type 1 (HIV-1) clinical outcomes but the underlying mechanisms are poorly understood. METHODS: We investigated the relationship between IL-10-promoter variants, plasma cytokine levels, immune responses and markers of disease outcome in antiretroviral-naïve HIV-1 chronically infected individuals from South Africa. Two IL-10-promoter single nucleotide polymorphisms (SNPs) were genotyped in 451 participants. Baseline plasma levels of select cytokines were measured for 112 individuals. Viral load, CD4(+) T-cell counts and HIV-1-specific interferon-gamma CD8(+) T-cell immune responses were measured at baseline. CD4(+) T-cell counts were measured longitudinally and rates of CD4(+) T-cell decline computed for 300 study subjects. RESULTS: The minor IL-10-1082G and -592A variants occurred at frequencies of 0.31 and 0.34, respectively. The -592AA genotype associated significantly with attenuated loss of CD4(+) T cells (P = .0496). Individuals possessing -1082GG had significantly higher IL-10 levels compared to -1082AA/AG (P = .0006). The -592AA genotype was associated with greater breadth of virus-specific CD8(+) T-cell responses compared to CC and CA (P = .002 and .004 respectively). CONCLUSIONS: IL-10-promoter variants may influence the rate of HIV-1 disease progression by regulating IL-10 levels and the breadth of CD8(+) T-cell immune responses.
Assuntos
Infecções por HIV/imunologia , HIV-1/imunologia , Interleucina-10/genética , Linfócitos T Citotóxicos/imunologia , Adulto , Contagem de Linfócito CD4 , Feminino , Genótipo , Infecções por HIV/sangue , Infecções por HIV/genética , Infecções por HIV/virologia , Humanos , Interferon gama/genética , Interferon gama/imunologia , Interleucina-10/sangue , Interleucina-10/imunologia , Masculino , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Estatísticas não Paramétricas , Carga ViralRESUMO
Interleukin (IL)-10 directly inhibits human immunodeficiency virus type 1 (HIV-1) replication, but it may also promote viral persistence by inactivation of effector immune mechanisms. Here, we show in an African cohort that individuals with genotypes associated with high IL-10 production at 2 promoter single-nucleotide polymorphisms (-1082 and -592) were less likely to become HIV-1 infected but had significantly higher median plasma viral loads during the acute phase (Assuntos
Infecções por HIV/genética
, HIV-1
, Interleucina-10/genética
, Polimorfismo Genético
, Regiões Promotoras Genéticas/genética
, Adulto
, Alelos
, Estudos de Coortes
, Feminino
, Predisposição Genética para Doença
, Genótipo
, Infecções por HIV/epidemiologia
, HIV-1/genética
, HIV-1/imunologia
, Humanos
, Estudos Longitudinais
, Mutação
, África do Sul/epidemiologia
, Carga Viral