Association of antigen-stimulated release of tumor necrosis factor-alpha in whole blood with response to chemotherapy in patients with pulmonary multidrug-resistant tuberculosis

Seok Yong Eum, Ye Jin Lee, Jin Hong Min, Hyun Kyung Kwak, Min Sun Hong, Ji Hye Kong, Soo Hee Hwang, Seung Kyu Park, Jason J. Leblanc, Laura E. Via, Clifton E. Barry, Sangnae Cho

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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. Conclusion: 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.

Original languageEnglish
Pages (from-to)275-284
Number of pages10
JournalRespiration
Volume80
Issue number4
DOIs
Publication statusPublished - 2010 Sep 1

Fingerprint

Multidrug-Resistant Tuberculosis
Pulmonary Tuberculosis
Tumor Necrosis Factor-alpha
Sputum
Antigens
Drug Therapy
Interleukin-12
Interleukin-10
Tuberculosis
Cytokines
Down-Regulation
Biomarkers
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

Cite this

Eum, Seok Yong ; Lee, Ye Jin ; Min, Jin Hong ; Kwak, Hyun Kyung ; Hong, Min Sun ; Kong, Ji Hye ; Hwang, Soo Hee ; Park, Seung Kyu ; Leblanc, Jason J. ; Via, Laura E. ; Barry, Clifton E. ; Cho, Sangnae. / Association of antigen-stimulated release of tumor necrosis factor-alpha in whole blood with response to chemotherapy in patients with pulmonary multidrug-resistant tuberculosis. In: Respiration. 2010 ; Vol. 80, No. 4. pp. 275-284.
@article{38102cb8f2db44efa3e822fb6999044c,
title = "Association of antigen-stimulated release of tumor necrosis factor-alpha in whole blood with response to chemotherapy in patients with pulmonary multidrug-resistant tuberculosis",
abstract = "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. Conclusion: 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.",
author = "Eum, {Seok Yong} and Lee, {Ye Jin} and Min, {Jin Hong} and Kwak, {Hyun Kyung} and Hong, {Min Sun} and Kong, {Ji Hye} and Hwang, {Soo Hee} and Park, {Seung Kyu} and Leblanc, {Jason J.} and Via, {Laura E.} and Barry, {Clifton E.} and Sangnae Cho",
year = "2010",
month = "9",
day = "1",
doi = "10.1159/000283687",
language = "English",
volume = "80",
pages = "275--284",
journal = "Respiration; international review of thoracic diseases",
issn = "0025-7931",
publisher = "S. Karger AG",
number = "4",

}

Association of antigen-stimulated release of tumor necrosis factor-alpha in whole blood with response to chemotherapy in patients with pulmonary multidrug-resistant tuberculosis. / Eum, Seok Yong; Lee, Ye Jin; Min, Jin Hong; Kwak, Hyun Kyung; Hong, Min Sun; Kong, Ji Hye; Hwang, Soo Hee; Park, Seung Kyu; Leblanc, Jason J.; Via, Laura E.; Barry, Clifton E.; Cho, Sangnae.

In: Respiration, Vol. 80, No. 4, 01.09.2010, p. 275-284.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association of antigen-stimulated release of tumor necrosis factor-alpha in whole blood with response to chemotherapy in patients with pulmonary multidrug-resistant tuberculosis

AU - Eum, Seok Yong

AU - Lee, Ye Jin

AU - Min, Jin Hong

AU - Kwak, Hyun Kyung

AU - Hong, Min Sun

AU - Kong, Ji Hye

AU - Hwang, Soo Hee

AU - Park, Seung Kyu

AU - Leblanc, Jason J.

AU - Via, Laura E.

AU - Barry, Clifton E.

AU - Cho, Sangnae

PY - 2010/9/1

Y1 - 2010/9/1

N2 - 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. Conclusion: 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.

AB - 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. Conclusion: 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.

UR - http://www.scopus.com/inward/record.url?scp=77957001852&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77957001852&partnerID=8YFLogxK

U2 - 10.1159/000283687

DO - 10.1159/000283687

M3 - Article

C2 - 20145387

AN - SCOPUS:77957001852

VL - 80

SP - 275

EP - 284

JO - Respiration; international review of thoracic diseases

JF - Respiration; international review of thoracic diseases

SN - 0025-7931

IS - 4

ER -