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)-alpha, interferon (IFN)-gamma, 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-alpha, IFN-gamma, 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-alpha mRNA were associated with a slower rate of disease progression, and TNF-alpha 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.
Than
S
S
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, New York 11030, USA.
Hu
R
R
Oyaizu
N
N
Romano
J
J
Wang
X
X
Sheikh
S
S
Pahwa
S
S
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D018450:Disease Progression; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis / Q000378:metabolism; D018664:Interleukin-12 / Q000096:biosynthesis / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism
D016207:Cytokines; D007376:Interleukin-2; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma