Free Content The immune response to Mycobacterium tuberculosis in HIV-infected and uninfected adults in Uganda: application of a whole blood cytokine assay in an epidemiological study

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Abstract:

SETTING: Out-patient clinic, Entebbe, Uganda.

BACKGROUND: It has been proposed that ‘type 1’ cytokines are essential in protective immunity to Mycobacterium tuberculosis and that suppression of ‘type 1’ or a switch to a ‘type 2’ profile is deleterious. We employed a simple assay to examine whether the dependence of the immunological responses to mycobacterial antigens on a range of explanatory factors could be determined in a population where tuberculosis is endemic.

OBJECTIVE: To determine the relationship between the tuberculin skin test response and cytokine profile, and the effect of human immunodeficiency virus (HIV) infection.

DESIGN: A cross-sectional study of 97 Ugandan adults (22 HIV-positive, 75 HIV-negative). Whole blood was stimulated in vitro using mycobacterial antigens (purified protein derivative [PPD] and culture filtrate proteins [CFP]). ‘Type 1’ cytokines (gamma interferon [IFN-γ] and interleukin-2 [IL-2]), ‘type 2’ cytokines (IL-5 and IL-10) and tumour necrosis factor alpha (TNF-α) were measured in culture supernatants.

RESULTS: Among HIV-negative subjects, a positive tuberculin skin test was associated with type 1 or mixed (type 1 + type 2) cytokine production, but a positive IFN-γ response also occurred in a proportion of tuberculin skin test negative subjects (36% for PPD, 17% for CFP). In association with HIV infection, IFN-γ responses to mycobacterial antigens were profoundly impaired (odds ratio [OR] 0.10 for PPD, 0.06 for CFP, P ≤ 0.001), but production of IL-2, IL-5 and TNF-α was relatively sustained, and IL-10 increased or sustained (OR 3.97 for PPD, P = 0.01, 1.14 for CFP, P = 0.99).

CONCLUSION: The type 1/type 2 cytokine balance was not defined by the tuberculin skin test response, and may have a closer relation to protective immunity. IFN-γ production was strikingly impaired in association with HIV infection, while production of type 2 cytokines was sustained or increased. Use of a simple assay allowed a large sample of subjects to be examined, producing epidemiologically meaningful results.

Keywords: HIV; Uganda; cytokines; tuberculosis

Document Type: Regular Paper

Affiliations: 1: Uganda Virus Research Institute, Entebbe, Uganda; and London School of Hygiene & Tropical Medicine, London, UK 2: London School of Hygiene & Tropical Medicine, London, UK 3: Uganda Virus Research Institute, Entebbe, Uganda

Publication date: March 1, 1999

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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