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Clinical and Diagnostic Laboratory Immunology, September 2002, p. 1049-1056, Vol. 9, No. 5
1071-412X/02/$04.00+0     DOI: 10.1128/CDLI.9.5.1049-1056.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Spontaneous Cytokine Production and Its Effect on Induced Production

Derrick Walker,1* Janine Jason,1 Kelly Wallace,1 Justin Slaughter,1 Virginia Whatley,1 Alison Han,1 Okey C. Nwanyanwu,2 Peter N. Kazembe,3 Hamish Dobbie,3 Lennox Archibald,4 and William R. Jarvis4

HIV Immunology and Diagnostics Branch, Division of AIDS, STD, and TB Laboratory Research,1 The Investigation and Prevention Branch, Hospital Infections Program, National Center for Infectious Diseases,4 The Office of Global Health, Centers for Disease Control and Prevention, Public Health Service, U.S. Department of Health and Human Services, Atlanta, Georgia 30333,2 and Lilongwe Central Hospital and Community Health Sciences Unit, Ministry of Health and Population, Lilongwe, Malawi3

Received 26 December 2001/ Returned for modification 22 April 2002/ Accepted 30 May 2002

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.

* Corresponding author. Mailing address: Mailstop A-25, DASTLR, NCID, CDC, 1600 Clifton Rd., N.E., Atlanta, GA 30333. Phone: (404) 639-0871. Fax: (404) 639-2108. E-mail: ziq4{at}cdc.gov.

Clinical and Diagnostic Laboratory Immunology, September 2002, p. 1049-1056, Vol. 9, No. 5
1071-412X/02/$04.00+0     DOI: 10.1128/CDLI.9.5.1049-1056.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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