Spontaneous cytokine production and its effect on induced production.
Cytokines regulate cellular immune activity and are produced by a variety of cells, especially lymphocytes, monocytes, and macrophages. Multiparameter flow cytometry is often used to examine cell-specific cytokine production after in vitro phorbol 12-myristate 13-acetate and ionomycin induction, with brefeldin A or other agents added to inhibit protein secretion. Spontaneous ex vivo production reportedly rarely occurs. We examined the spontaneous production of interleukin 2 (IL-2), IL-4, IL-6, IL-8, IL-10, tumor necrosis factor alpha (TNF-alpha), and gamma interferon (IFN-gamma) by peripheral-blood B lymphocytes, T cells, CD8(-) T cells, CD8(+) T cells, CD3(-) CD16/56(+) lymphocytes (natural killer [NK] cells), CD3(+) CD16/56(+) lymphocytes (natural T [NT] cells), and/or monocytes of 316 acutely ill hospitalized persons and 62 healthy adults in Malawi, Africa. We also evaluated the relationship between spontaneous and induced cytokine production. In patients, spontaneous TNF-alpha production occurred most frequently, followed in descending order by IFN-gamma, IL-8, IL-4, IL-10, IL-6, and IL-2. Various cells of 60 patients spontaneously produced TNF-alpha; for 12 of these patients, TNF-alpha was the only cytokine produced spontaneously. Spontaneous cytokine production was most frequent in the immunoregulatory cells, NK and NT. For IL-2, IL-4, IL-6, IL-8, and IL-10, spontaneous cytokine production was associated with greater induced production. For TNF-alpha and IFN-gamma, the relationships varied by cell type. For healthy adults, IL-6 was the cytokine most often produced spontaneously. Spontaneous cytokine production was not unusual in these acutely ill and healthy persons living in an area where human immunodeficiency virus, mycobacterial, malaria, and assorted parasitic infections are endemic. In such populations, spontaneous, as well as induced, cell-specific cytokine production should be measured and evaluated in relation to various disease states.
Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia 30333, USA. ziq4@cdc.gov
Derrick
D
Walker
Janine
J
Jason
Kelly
K
Wallace
Justin
J
Slaughter
Virginia
V
Whatley
Alison
A
Han
Okey C
OC
Nwanyanwu
Peter N
PN
Kazembe
Hamish
H
Dobbie
Lennox
L
Archibald
William R
WR
Jarvis
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma