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 production profiles switch from predominantly type 1 (interleukin-2 [IL-2] and gamma interferon [IFN-gamma]) to type 2 (IL-4 and IL-10) cytokines with disease progression. To test this hypothesis in vertically HIV-infected children, we measured cytokine transcription and production in rapid progressors (RPs), seroreverters (SRs), and those children exposed to HIV in utero (P0s). Production of type 1 and type 2 cytokines was measured in peripheral blood mononuclear cell cultures of 8 SR, 25 P0, and 11 RP children. Unstimulated cultures, irrespective of infection and stage of disease, produced similar levels of IL-2, IFN-gamma, IL-4, and IL-10. Upon stimulation with phytohemagglutinin (PHA) plus phorbol-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 significantly less IFN-gamma mRNA (P < 0.01) than SR children. RP children expressed significantly higher levels of IL-4 mRNA than P0 children (P < 0.03). There were no differences in the production of IL-10 by PHA-PMA-stimulated peripheral blood mononuclear cell cultures among the three groups of children. Our data with these pediatric patients suggest that a deficiency in mitogen-stimulated type 1 cytokine production and excess type 2 cytokine (IL-4) transcription correlate with disease progression. Additional studies with larger sample sizes are needed to test further the hypothesis of the type 1-to-type 2 cytokine switch in children infected with HIV.
Lee
B N
BN
Division of Laboratory Medicine, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Lu
J G
JG
Kline
M W
MW
Paul
M
M
Doyle
M
M
Kozinetz
C
C
Shearer
W T
WT
Reuben
J M
JM
D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000145:classification; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000378:metabolism
D016207:Cytokines; D007376:Interleukin-2; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma