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.
METHODS
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.


METHODS
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-gamma] and interleukin-2 [IL-2]), 'type 2' cytokines (IL-5 and IL-10) and tumour necrosis factor alpha (TNF-alpha) 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-gamma response also occurred in a proportion of tuberculin skin test negative subjects (36% for PPD, 17% for CFP). In association with HIV infection, IFN-gamma responses to mycobacterial antigens were profoundly impaired (odds ratio [OR] 0.10 for PPD, 0.06 for CFP, P< or =0.001), but production of IL-2, IL-5 and TNF-alpha was relatively sustained, and IL-10 increased or sustained (OR 3.97 for PPD, P = 0.01, 1.14 for CFP, P = 0.99).


CONCLUSIONS
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-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, producing epidemiologically meaningful results.
Elliott
A M
AM
Uganda Virus Research Institute, Entebbe. mrc@starcom.co.ug
Hurst
T J
TJ
Balyeku
M N
MN
Quigley
M A
MA
Kaleebu
P
P
French
N
N
Biryahwaho
B
B
Whitworth
J A
JA
Dockrell
H M
HM
Hayes
R J
RJ
D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood*; D005240:Feasibility Studies; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007371:Interferon-gamma / Q000097:blood; D007378:Interleukins / Q000097:blood; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016036:Seroepidemiologic Studies; D014374:Tuberculin Test; D014376:Tuberculosis / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D014454:Uganda / Q000453:epidemiology
D000942:Antigens, Bacterial; D016207:Cytokines; D007378:Interleukins; D007371:Interferon-gamma