Cytokine pattern in relation to disease progression in human immunodeficiency virus-infected children

Cytokine mRNA expression and stimulus-induced cytokines were examined in peripheral blood mononuclear cells in 62 human immunodeficiency virus (HIV)- infected children and uninfected controls. Compared with that in controls, constitutive mRNA expression in patients was increased for tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-10 and decreased for IL-12; it was undetectahle for IL-2 and IL-4 in both patients and controls. Stimulus-induced secretion of TNF-α, IFN-γ, IL-12, and IL-4 was less than that in controls; IL-10 secretion was similar. There was no increase in stimulus-induced or constitutive IL-4 or IL-10 in children with severe immunologic deficit compared with controls. A higher stimulus-induced IL-10 secretion and a lower constitutive TNF-α mRNA were associated with a slower rate of disease progression, and TNF-α mRNA expression correlated with lower plasma HIV RNA. Thus, constitutive cytokine mRNA expression differs from stimulus-induced cytokine responses. The dominant defect in HIV- infected children appears to be one of reduced type 1 cytokines, predominantly IL-2.