Association of antigen-stimulated release of tumor necrosis factor-alpha in whole blood with response to chemotherapy in patients with pulmonary multidrug-resistant tuberculosis.
BACKGROUND
We have previously reported that TNF-α levels correlate to total mycobacterial burden in tuberculosis (TB) patients.


OBJECTIVE
To characterize the dynamics of cytokine responses in TB patients during chemotherapy to identify potential surrogate markers for effective treatment.


METHODS
Following induction by culture filtrate proteins in whole blood, production patterns of TNF-α, IL-10, IFN-γ and IL-12 were measured in 23 non-multidrug-resistant (MDR)-TB and 16 MDR-TB patients and in 31 healthy controls. Rates of mycobacterial clearance from the sputum were then measured and compared.


RESULTS
Prior to the initiation of chemotherapy, TNF-α and IL-10 levels were significantly higher in TB patients than in healthy controls while IFN-γ and IL-12 levels were similar. During chemotherapy, the levels of all 4 cytokines increased. We evaluated these responses separately in patients that did and did not clear their sputum culture at 2 and 6 months. At 2 months, decreases in both IFN-γ and IL-12 correlated strongly with a successful early response, while after 6 months of therapy, when half (7/14) of MDR-TB patients were still sputum culture positive, downregulation of TNF-α was uniquely correlated with sputum conversion between the groups.


CONCLUSIONS
Our findings suggest the possibility that the regulation of TNF-α production in whole blood may be a more specific indicator of sputum conversion at 6 months than IFN-γ, IL-12 or IL-10 in MDR-TB patients.
Division of Immunopathology and Cellular Immunology, and of Molecular Microbiology, International Tuberculosis Research Center, Masan, Republic of Korea. syeumkr @ gmail.com
Seok-Yong
SY
Eum
Ye-Jin
YJ
Lee
Jin-Hong
JH
Min
Hyun-Kyung
HK
Kwak
Min-Sun
MS
Hong
Ji-Hye
JH
Kong
Soo-Hee
SH
Hwang
Seung-Kyu
SK
Park
Jason J
JJ
Leblanc
Laura E
LE
Via
Clifton E
CE
Barry
Sang-Nae
SN
Cho
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification*; D013183:Sputum / Q000382:microbiology*; D018088:Tuberculosis, Multidrug-Resistant / Q000097:blood* / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D055815:Young Adult
D000995:Antitubercular Agents; D015415:Biomarkers; C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma