Cytokine Pattern in Relation to Disease Progression in Human Immunodeficiency Virus--Infected Children

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Abstract
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 undetectable 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.

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