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

SETTING: Out-patient clinic, Entebbe, Uganda. BACKGROUND: It has been proposed that 'type 1' cytokines are essential in p rotective immunity to Mycobacterium tuberculosis and that suppression of 't ype 1' or a switch to a 'type 2' profile is deleterious. We employed a simp le assay to examine whether the dependence of the immunological responses t o mycobacterial antigens on a range of explanatory factors could be determi ned in a population where tuberculosis is endemic. OBJECTIVE: To determine the relationship between the tuberculin skin test r esponse and cytokine profile, and the effect of human immunodeficiency viru s (HIV) infection. DESIGN: A cross-sectional study of 97 Ugandan adults (22 HIV-positive, 75 H IV-negative). Whole blood was stimulated in vitro using mycobacterial antig ens (purified protein derivative [PPD] and culture filtrate proteins [CFP]) . Type 1' cytokines (gamma interferon [IFN-gamma] and interleukin-2 [IL-2]) , 'type 2' cytokines (IL-5 and IL-10) and tumour necrosis factor alpha (TNF -a) were measured in culture supernatants. RESULTS: Among HIV-negative subjects, a positive tuberculin skin test was a ssociated with type 1 or mixed (type 1 + type 2) cytokine production, but a positive IFN-gamma response also occurred in a proportion of tuberculin sk in test negative subjects (36% for PPD, 17% for CFP). In association with H IV infection, IFN-gamma responses to mycobacterial antigens were profoundly impaired (odds ratio [OR] 0.10 for PPD, 0.06 for CFP, P less than or equal to 0.001), but production of IL-2, IL-5 and TNF-a 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 tuber culin skin test response, and may have a closer relation to protective immu nity. IFN-gamma 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, p roducing epidemiologically meaningful results.