TYPE-1 AND TYPE-2 CYTOKINE PROFILES IN CHILDREN EXPOSED TO OR INFECTED WITH VERTICALLY TRANSMITTED HUMAN-IMMUNODEFICIENCY-VIRUS

In human immunodeficiency virus (HIV)-infected adults, cytokine produc tion profiles switch from predominantly type 1 (interleukin-2 [IL-2] a nd gamma interferon [IFN-gamma]) to type 2 (IL-4 and IL-10) cytokines with disease progression, To test this hypothesis in vertically HIV-in fected children, we measured cytokine transcription and production in rapid progressors (RPs), seroreverters (SRs), and those children expos ed to HIV in utero (P0s), Production of type 1 and type 2 cytokines wa s measured in peripheral blood mononuclear cell cultures of 8 SR, 25 P 0, and 11 RP children, Unstimulated cultures, irrespective of infectio n and stage of disease, produced similar levels of IL-2, IFN-gamma, IL -4, and IL-10, Upon stimulation with phytohemagglutinin (PHA) plus pho rbol-12-myristate-13-acetate (PMA), RP children produced less IL-2 (P < 0.01) and IFN-gamma (P < 0.02) than SR children and also expressed s ignificantly less IFN-gamma mRNA (P < 0.01) than SR children, RP child ren expressed significantly higher levels of IL-4 mRNA than P0 childre n (P < 0.03), There were no differences in the production of IL-10 by PHA-PMA-stimulated peripheral blood mononuclear cell cultures among th e three groups of children, Our data with these pediatric patients sug gest that a deficiency in mitogen-stimulated type 1 cytokine productio n and excess type 2 cytokine (IL-4) transcription correlate with disea se progression, Additional studies with larger sample sizes are needed to test further the hypothesis of the type 1-to-type 2 cytokine switc h in children infected with HIV.