title: Peripheral blood cell-specific cytokines in persons with untreated HIV infection in Malawi, Africa.
abstract: Human immunodeficiency virus (HIV) infection is the primary cause of morbidity and mortality in Malawi, Africa, because of its many effects on the immune system. Immune cells communicate through cytokines; therefore, we examined the relationships between HIV serostatus and cell-specific cytokine production for 40 asymptomatic, employed adults and 312 acutely ill, hospitalized patients in Malawi. We also measured the plasma HIV-1 RNA levels of 13 asymptomatic persons and 83 patients found to be HIV(+). We incubated peripheral whole blood with brefeldin-A +/- phorbol 12-myristate 13-acetate and ionomycin and then permeabilized, fixed, fluorescently stained, and examined the mononuclear cells with four-color, six-parameter flow cytometry. The percentage of lymphocytes expressing CD4 did not differ significantly between the HIV(+) and HIV(-) healthy adults (medians, 35.2 vs. 40.8%, respectively), but a wide array of cytokine parameters were lower in the HIV(+) than in the HIV(-) asymptomatic persons, for example, median percentages of T cells producing induced interleukin 2 (IL-2) (8.7 vs. 16.5%, respectively) and spontaneously producing IL-6 (0.7 vs. 11.0%, respectively). Also, four T cell parameters reflecting type 2-to-type 1 cytokine balances (T2/T1) were higher in the HIV(+), versus HIV(-), asymptomatic persons. Unlike the healthy adults, for patients with mycobacteremia/fungemia or malaria, the HIV(+) patients had higher median percentages of T cells and CD8(+) T cells producing induced interferon gamma than did the HIV(-) PATIENTS: For both asymptomatic and acutely ill persons, HIV-1 plasma levels were positively correlated with T2/T1 parameters. Cell-specific cytokine effects of HIV infection may precede measurable effects on CD4 expression. Cytokine therapies, even beyond periodic administration of IL-2, may improve the responses of HIV-infected persons to both HIV and coinfections.
authors.affiliation: HIV Immunology and Diagnostics Branch, Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. zlk1@cdc.gov
authors.forename: Julie A
authors.initials: JA
authors.lastname: Chatt
authors.forename: Janine
authors.initials: J
authors.lastname: Jason
authors.forename: Okey C
authors.initials: OC
authors.lastname: Nwanyanwu
authors.forename: Lennox K
authors.initials: LK
authors.lastname: Archibald
authors.forename: Bharat
authors.initials: B
authors.lastname: Parekh
authors.forename: Peter N
authors.initials: PN
authors.lastname: Kazembe
authors.forename: Hamish
authors.initials: H
authors.lastname: Dobbie
authors.forename: William R
authors.initials: WR
authors.lastname: Jarvis
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D005434:Flow Cytometry; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008295:Malawi; D008297:Male; D012367:RNA, Viral / Q000097:blood; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; D015483:HIV Antibodies; D012367:RNA, Viral