Increased Th1 and Th2 type cytokine production in patients with active tuberculosis.
BACKGROUND
The global spread of tuberculosis necessitates the development of an effective vaccine and new treatment modalities. That requires a better understanding of the differences in regulation of the immune responses to Mycobacterium tuberculosis between individuals who are susceptible or resistant to the infection. Previous immune studies in young Ethiopian immigrants to Israel did not demonstrate anergy to purified protein derivative or a Th2-like cytokine profile.


OBJECTIVE
To evaluate the profile of Th1 and Th2 cytokine production in immigrant TB patients, in comparison with asymptomatic control subjects.


METHODS
The present study included (part 1): 39 patients with acute TB (group 1), 34 patients with chronic relapsing TB (group 2), 39 Mantoux-positive asymptomatic TB contacts (group 3), and 21 Mantoux-negative asymptomatic controls (group 4). Patients were mainly immigrants from Eastern Europe and Ethiopia. Levels of interferon gamma, interleukin 2 receptor, IL-6 and IL-10 were measured in serum and in non-stimulated and PPD-stimulated peripheral blood mononuclear cell culture supernatants, using commercial ELISA kits. In addition (part 2), levels of IFNgamma and IL-12p40 were evaluated in 31 immigrant Ethiopian patients and 58 contact family members.


RESULTS
Patients with acute disease tended to secrete more cytokines than contacts, and contacts more than chronic patients and controls, without a specific bias. None of the patients showed in vitro anergy. Discriminant probability analysis showed that from the total of 12 available parameters, a cluster of 6 (IFNgamma-SER, IFNgamma-PPD, IL-2R-SER, IL-10-SER, IL-10-NS and IL-6-PPD) predicted an 84% probability to become a TB contact upon exposure, 71% a chronic TB patient and 61% an acute TB patient. Family-specific patterns of IFNgamma were demonstrated in the second part of the study.


CONCLUSIONS
Firstly, no deficiency in cytokine production was demonstrated in TB patients. Secondly, acute TB patients secreted more cytokines than contacts, and contacts more than unexposed controls. Thus, neither anergy nor a cytokine dysregulation explains susceptibility to acute TB disease in our cohort, although chronic TB patients produced less cytokines than did acute patients and less than asymptomatic contacts. Thirdly, a certain cytokine configuration may predict a trend of susceptibility to acquire, or not acquire, clinical TB. It is presently unclear whether this finding may explain the disease spread in large populations. Finally, the familial association of IFNgamma secretion levels probably points towards a genetic regulation of the immune response to Mycobacterium tuberculosis.
Handzel
Zeev T
ZT
Pediatric Research Institute, Kaplan Medical Center, Rehovot, Israel. zthandzel@clalit.org.il
Barak
Vivian
V
Altman
Yehudith
Y
Bibi
Haim
H
Lidgi
Moshe
M
Iancovici-Kidon
Mona
M
Yassky
Dov
D
Raz
Meir
M
D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D004641:Emigration and Immigration; D005002:Ethiopia / Q000208:ethnology; D005061:Europe, Eastern / Q000208:ethnology; D006801:Humans; D007371:Interferon-gamma; D016753:Interleukin-10; D007376:Interleukin-2; D015850:Interleukin-6; D007557:Israel; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000473:pathology*; D018418:Th2 Cells / Q000473:pathology*; D014376:Tuberculosis / Q000208:ethnology / Q000276:immunology* / Q000503:physiopathology*
D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D016753:Interleukin-10; D007371:Interferon-gamma