Th1 and Th2 cytokine response in patients with pulmonary tuberculosis and health care workers occupationally exposed to M. tuberculosis.
Aiming to detect reliable markers indicating protection from or susceptibility to tuberculosis infection, we investigated both Th1/Th2 cytokines and total IgE plasma levels in health care workers occupationally exposed to M. tuberculosis, in patients with pulmonary tuberculosis and in healthy persons.


METHODS
The study groups have included 15 health care workers in close contact with TB patients, patients with active pulmonary tuberculosis at diagnosis and after treatment (12 advanced and 10 moderate TB, of which 6 had also pleurisy) and 20 healthy volunteers. Peripheral blood mononuclear cells (PBMC) were stimulated with PPD for 7 days and the release of six cytokines (IL-2, IFN-gamma, TNFalpha, IL-4, IL-5, IL-10) was simultaneously quantified by cytometric bead array (CBA) in culture supernatants. The same method was used to determine the cytokine level in plasma and pleural effusions from TB patients. Six neoplastic pleurisies were included in this investigation as a control group. Total plasma IgE level was measured by chemiluminescence technique.


RESULTS
Plasma and pleural fluid cytokine analysis at the outset of tuberculosis disease reflect the same Th1 response dominated by IFN-gamma. In opposition, very low IFN-gamma levels were recorded in neoplastic pleural fluids. Both types of cytokines (Th1 and Th2) were secreted in response to in vitro PPD stimulation of PBMCs and had different evolution in moderate and advanced TB. Thus, IFN-gamma, TNFalpha, IL-4, and IL5 production after 6 months-treatment decreased in moderate TB and increased in severe disease (p < 0.05). Moreover, total IgE plasma levels were higher than the normal value (87 IU/ml) in health care workers and significant amounts were recorded in patients, especially in advanced TB after 6 months of treatment (p = 0.00).


CONCLUSIONS
Our results confirm that the quantification of IFNă could be a good marker for the diagnosis of TB pleural effusions but raised the question whether plasma IgE levels might be a reliable marker indicating the transition to disease. Further studies are needed to understand the complex interaction between pro- and anti-inflammatory cytokines that might play an Key words: TUBERCULOSIS, CYTOKINES,
Cozmei
Carmen
C
Institute of Public Health Iaşi, Department of Occupational Medicine, Gr. T. Popa University of Medicine and Pharmacy Iaşi.
Constantinescu
Daniela
D
Carasevici
E
E
Anisie
Ecaterina
E
Ungureanu
Didona
D
Sorete-Arbore
Adriana
A
Gramadă
Doina
D
Mihăescu
Tr
T
Croitoru
Carmen
C
Popa
Doina
D
D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006282:Health Personnel; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D016898:Interferon-alpha / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D049449:Luminescence; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016273:Occupational Exposure; D010996:Pleural Effusion / Q000276:immunology; D012383:Romania; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology*
D015415:Biomarkers; D016207:Cytokines; D016898:Interferon-alpha; D007073:Immunoglobulin E; D007371:Interferon-gamma