Clinical relevance of cytokine production in HIV-1 infection in children on antiretroviral therapy

In order to investigate the correlation among cytokine production and antir etroviral therapy (ART), viral load, CD4(+) and CD8(+) T lymphocytes, 55 hu man immunodeficiency virus (HIV)-1-infected children on ART or not, and 16 uninfected controls were studied. Peripheral blood mononuclear cells (PBMCs ) of HIV-1-infected children and controls were cultured and spontaneous and mitogen-stimulated cytokines production was quantified in the supernatants . Viral load was quantified using standard molecular assay. CD4 and CD8 T-l ymphocyte counts were determined by flow cytometry. Cytokine production by mitogen-stimulated PBMCs showed different profiles in HIV-1 children whethe r treated or not. The tumour necrosis factor (TNF)-alpha production was hig her and the interleukin (IL)-10 production was lower in the HIV-1-untreated group than in the HIV-1-treated children and controls. The IL-2 production was reduced and the RANTES production was higher in both HIV-1 groups comp ared with the controls. The interferon (IFN)-gamma and the IL-5 production was significantly reduced in the HIV-1-treated children compared to the con trols. Interestingly, the analysis of the correlation of HIV-1 phenotype wi th cytokine production indicated an increased RANTES production in relation to nonsyncytium-inducing viral phenotype with slow/low replication profile , whereas decreased IL-10 levels was associated to syncytium-inducing (SI) strains and rapid/high replication. Our findings suggest that AVT changes o n the cytokine and chemokine production play an important role in the HIV p athogenesis.