Disruption in cytokine and chemokine production by T-cells in vertically HIV-1-infected children

This study measured cytokine production by mitogen-stimulated peripheral bl ood mononuclear cells (PBMCs) from 55 human immunodeficiency virus (HIV)-in fected children born to HIV-infected mothers, and compared it with vertical ly exposed but uninfected age-matched children. A significant defect was ob served in Th, cytokine production [interferon-gamma, and interleukin-2 (IL- 2)] in HIV-infected children compared with controls, but without a concomit ant increase in Th-2 cytokines. Indeed, IL-5 and IL-10 production was even lower in HIV-infected children than in controls, with the decrease in IL-5 being the best predictive marker of immunodeficiency. In addition, an incre ased release of tumour necrosis factor-alpha (TNF-alpha) that correlated we ll with CD4(+) levels, and a positive correlation of the TNF-alpha /IL-10 r atio with disease progression was observed. A correlation between AIDS-free status and higher %CD4(+) and %CD8(+) T-lymphocytes and RANTES (regulated on activation, normal T-cell expressed and secreted) production was also fo und. Conclusion: A dysfunctional cytokine production of PBMCs was observed in HI V-infected children in both Th, and Th2 cytokines due to quantitative and q ualitative defects induced by HIV-1. An important observation was an increa sed RANTES production associated with viral isolates of NSI/R5 phenotype an d S/L kinetics.