The Patterns of Interferon-Gamma and Interleukin-10 Production as a Potential Immunological Biomarker for the Outcome of Mycobacterium Tuberculosis Infection

Benson Olu Akinshipe; Friday Alfred Ehiaghe; Anthony Chukwuka Nwaobi; Emmanuel Babatunde Adedeji; Herbert Obi Okpala

doi:doi:10.11648/j.iji.20170506.12

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The Patterns of Interferon-Gamma and Interleukin-10 Production as a Potential Immunological Biomarker for the Outcome of Mycobacterium Tuberculosis Infection

Benson Olu Akinshipe, Friday Alfred Ehiaghe, Anthony Chukwuka Nwaobi, Emmanuel Babatunde Adedeji, Herbert Obi Okpala

Published in International Journal of Immunology (Volume 5, Issue 6)

Received: 5 December 2017 Accepted: 13 December 2017 Published: 16 January 2018

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Abstract

Deficiencies in current tuberculosis (TB) immunodiagnostics pipeline demand new approaches to control TB. Because the balance in key pro- and anti-inflammatory cytokines production could determine Mycobacterium Tuberculosis (MTb) infection outcome, this study aimed to determine the patterns of MTb-specific antigen-stimulated Interferon-gamma (IFN-y) and Interleukin-10 (IL-10) production in different clinical forms of MTb infection and to evaluate their concomitant changes during anti-TB treatment (ATT). Overall, 84 BCG-vaccinated HIV-negative adults, consisting of 25 Healthy Community Controls (HCC), 27 Latent Tuberculosis Infection (LTBI) cases, and a cohort of 32 Acute Pulmonary Tuberculosis (APTB) patients were investigated for IFN-y and IL-10 responses at enrollment (base-line) and during ATT at 2-month (ATT1) and 6-month (ATT2). At enrollment, groups didn’t differ significantly in age, gender, or CD4+ T counts but differed in the other socio-demographics, and hematological parameters, p<0.05. Base-line Sandwich ELISA – measured IFN-y responses were significantly higher in HCC (223.50±58.11pg/ml) compared with LTBI (128.82±41.81pg/ml) and APTB (47.82±22.05pg/ml), p<0.0001 in each case. During treatment, IFN-y levels increased significantly at ATT1 (125.37±16.09pg/ml) and ATT2 (203.35±23.24pg/ml), p<0.0001. Conversely, base-line IL-10 responses increased significantly in APTB (17.53±6.30pg/ml), compared with LTBI (10.71±2.39pg/ml) and HCC (7.49±2.02pg/ml), P<0.0001, but declined significantly at ATT1 (10.54±2.25pg/ml) and ATT2 (5.25±1.45pg/ml), P=<0.0001. Cytokines response combination ratio showed: ‘High’ HCC, ‘Intermediate’ LTBI, or ‘Low’ APTB ratio that increased during successful ATT; the two identified MDR-TB patients recorded fluctuating but constantly low ratio during ATT. These results demonstrate the immunocompetence of MTb-exposed adults, and that IFN-y and IL-10 cytokines cross-regulate, and strongly suggest a shift toward IFN-y-mediated pro-inflammatory host immune phenotype during effective control of MTb infection. The IFN-y/IL-10 response ratio is a novel potential immunological biomarker to assess if MTb infection is going to resolve, result in latency, progress to TB; or become drug-resistant.

Published in	International Journal of Immunology (Volume 5, Issue 6)
DOI	10.11648/j.iji.20170506.12
Page(s)	97-105
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2018. Published by Science Publishing Group

Keywords

Adults, Mycobacterium Tuberculosis Infection, Immunodiagnostics, Cytokines Production Ratio, TB Control

References

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Benson Olu Akinshipe, Friday Alfred Ehiaghe, Anthony Chukwuka Nwaobi, Emmanuel Babatunde Adedeji, Herbert Obi Okpala. (2018). The Patterns of Interferon-Gamma and Interleukin-10 Production as a Potential Immunological Biomarker for the Outcome of Mycobacterium Tuberculosis Infection. International Journal of Immunology, 5(6), 97-105. https://doi.org/10.11648/j.iji.20170506.12

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ACS Style

Benson Olu Akinshipe; Friday Alfred Ehiaghe; Anthony Chukwuka Nwaobi; Emmanuel Babatunde Adedeji; Herbert Obi Okpala. The Patterns of Interferon-Gamma and Interleukin-10 Production as a Potential Immunological Biomarker for the Outcome of Mycobacterium Tuberculosis Infection. Int. J. Immunol. 2018, 5(6), 97-105. doi: 10.11648/j.iji.20170506.12

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AMA Style

Benson Olu Akinshipe, Friday Alfred Ehiaghe, Anthony Chukwuka Nwaobi, Emmanuel Babatunde Adedeji, Herbert Obi Okpala. The Patterns of Interferon-Gamma and Interleukin-10 Production as a Potential Immunological Biomarker for the Outcome of Mycobacterium Tuberculosis Infection. Int J Immunol. 2018;5(6):97-105. doi: 10.11648/j.iji.20170506.12

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@article{10.11648/j.iji.20170506.12,
  author = {Benson Olu Akinshipe and Friday Alfred Ehiaghe and Anthony Chukwuka Nwaobi and Emmanuel Babatunde Adedeji and Herbert Obi Okpala},
  title = {The Patterns of Interferon-Gamma and Interleukin-10 Production as a Potential Immunological Biomarker for the Outcome of Mycobacterium Tuberculosis Infection},
  journal = {International Journal of Immunology},
  volume = {5},
  number = {6},
  pages = {97-105},
  doi = {10.11648/j.iji.20170506.12},
  url = {https://doi.org/10.11648/j.iji.20170506.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.iji.20170506.12},
  abstract = {Deficiencies in current tuberculosis (TB) immunodiagnostics pipeline demand new approaches to control TB. Because the balance in key pro- and anti-inflammatory cytokines production could determine Mycobacterium Tuberculosis (MTb) infection outcome, this study aimed to determine the patterns of MTb-specific antigen-stimulated Interferon-gamma (IFN-y) and Interleukin-10 (IL-10) production in different clinical forms of MTb infection and to evaluate their concomitant changes during anti-TB treatment (ATT). Overall, 84 BCG-vaccinated HIV-negative adults, consisting of 25 Healthy Community Controls (HCC), 27 Latent Tuberculosis Infection (LTBI) cases, and a cohort of 32 Acute Pulmonary Tuberculosis (APTB) patients were investigated for IFN-y and IL-10 responses at enrollment (base-line) and during ATT at 2-month (ATT1) and 6-month (ATT2). At enrollment, groups didn’t differ significantly in age, gender, or CD4+ T counts but differed in the other socio-demographics, and hematological parameters, p<0.05. Base-line Sandwich ELISA – measured IFN-y responses were significantly higher in HCC (223.50±58.11pg/ml) compared with LTBI (128.82±41.81pg/ml) and APTB (47.82±22.05pg/ml), p<0.0001 in each case. During treatment, IFN-y levels increased significantly at ATT1 (125.37±16.09pg/ml) and ATT2 (203.35±23.24pg/ml), p<0.0001. Conversely, base-line IL-10 responses increased significantly in APTB (17.53±6.30pg/ml), compared with LTBI (10.71±2.39pg/ml) and HCC (7.49±2.02pg/ml), P<0.0001, but declined significantly at ATT1 (10.54±2.25pg/ml) and ATT2 (5.25±1.45pg/ml), P=<0.0001. Cytokines response combination ratio showed: ‘High’ HCC, ‘Intermediate’ LTBI, or ‘Low’ APTB ratio that increased during successful ATT; the two identified MDR-TB patients recorded fluctuating but constantly low ratio during ATT. These results demonstrate the immunocompetence of MTb-exposed adults, and that IFN-y and IL-10 cytokines cross-regulate, and strongly suggest a shift toward IFN-y-mediated pro-inflammatory host immune phenotype during effective control of MTb infection. The IFN-y/IL-10 response ratio is a novel potential immunological biomarker to assess if MTb infection is going to resolve, result in latency, progress to TB; or become drug-resistant.},
 year = {2018}
}

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TY  - JOUR
T1  - The Patterns of Interferon-Gamma and Interleukin-10 Production as a Potential Immunological Biomarker for the Outcome of Mycobacterium Tuberculosis Infection
AU  - Benson Olu Akinshipe
AU  - Friday Alfred Ehiaghe
AU  - Anthony Chukwuka Nwaobi
AU  - Emmanuel Babatunde Adedeji
AU  - Herbert Obi Okpala
Y1  - 2018/01/16
PY  - 2018
N1  - https://doi.org/10.11648/j.iji.20170506.12
DO  - 10.11648/j.iji.20170506.12
T2  - International Journal of Immunology
JF  - International Journal of Immunology
JO  - International Journal of Immunology
SP  - 97
EP  - 105
PB  - Science Publishing Group
SN  - 2329-1753
UR  - https://doi.org/10.11648/j.iji.20170506.12
AB  - Deficiencies in current tuberculosis (TB) immunodiagnostics pipeline demand new approaches to control TB. Because the balance in key pro- and anti-inflammatory cytokines production could determine Mycobacterium Tuberculosis (MTb) infection outcome, this study aimed to determine the patterns of MTb-specific antigen-stimulated Interferon-gamma (IFN-y) and Interleukin-10 (IL-10) production in different clinical forms of MTb infection and to evaluate their concomitant changes during anti-TB treatment (ATT). Overall, 84 BCG-vaccinated HIV-negative adults, consisting of 25 Healthy Community Controls (HCC), 27 Latent Tuberculosis Infection (LTBI) cases, and a cohort of 32 Acute Pulmonary Tuberculosis (APTB) patients were investigated for IFN-y and IL-10 responses at enrollment (base-line) and during ATT at 2-month (ATT1) and 6-month (ATT2). At enrollment, groups didn’t differ significantly in age, gender, or CD4+ T counts but differed in the other socio-demographics, and hematological parameters, p<0.05. Base-line Sandwich ELISA – measured IFN-y responses were significantly higher in HCC (223.50±58.11pg/ml) compared with LTBI (128.82±41.81pg/ml) and APTB (47.82±22.05pg/ml), p<0.0001 in each case. During treatment, IFN-y levels increased significantly at ATT1 (125.37±16.09pg/ml) and ATT2 (203.35±23.24pg/ml), p<0.0001. Conversely, base-line IL-10 responses increased significantly in APTB (17.53±6.30pg/ml), compared with LTBI (10.71±2.39pg/ml) and HCC (7.49±2.02pg/ml), P<0.0001, but declined significantly at ATT1 (10.54±2.25pg/ml) and ATT2 (5.25±1.45pg/ml), P=<0.0001. Cytokines response combination ratio showed: ‘High’ HCC, ‘Intermediate’ LTBI, or ‘Low’ APTB ratio that increased during successful ATT; the two identified MDR-TB patients recorded fluctuating but constantly low ratio during ATT. These results demonstrate the immunocompetence of MTb-exposed adults, and that IFN-y and IL-10 cytokines cross-regulate, and strongly suggest a shift toward IFN-y-mediated pro-inflammatory host immune phenotype during effective control of MTb infection. The IFN-y/IL-10 response ratio is a novel potential immunological biomarker to assess if MTb infection is going to resolve, result in latency, progress to TB; or become drug-resistant.
VL  - 5
IS  - 6
ER  -

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Author Information

Benson Olu Akinshipe

Departments of Medical Microbiology, School of Clinical Medicine, College of Health Sciences, Igbinedion University & Igbinedion University Teaching Hospital, Okada, Nigeria
Friday Alfred Ehiaghe

Department of Hematology, College of Health Sciences, Igbinedion University, Okada, Nigeria
Anthony Chukwuka Nwaobi

Department of Chemical Pathology, School of Clinical Medicine, College of Health Sciences, Igbinedion University, Okada, Nigeria
Emmanuel Babatunde Adedeji

Environmental Biology Research Unit, University of Ibadan, Ibadan, Nigeria
Herbert Obi Okpala

Department of Medical Laboratory Science, College of Health Sciences, Igbinedion University, Okada, Nigeria

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Benson Olu Akinshipe, Friday Alfred Ehiaghe, Anthony Chukwuka Nwaobi, Emmanuel Babatunde Adedeji, Herbert Obi Okpala. (2018). The Patterns of Interferon-Gamma and Interleukin-10 Production as a Potential Immunological Biomarker for the Outcome of Mycobacterium Tuberculosis Infection. International Journal of Immunology, 5(6), 97-105. https://doi.org/10.11648/j.iji.20170506.12

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ACS Style

Benson Olu Akinshipe; Friday Alfred Ehiaghe; Anthony Chukwuka Nwaobi; Emmanuel Babatunde Adedeji; Herbert Obi Okpala. The Patterns of Interferon-Gamma and Interleukin-10 Production as a Potential Immunological Biomarker for the Outcome of Mycobacterium Tuberculosis Infection. Int. J. Immunol. 2018, 5(6), 97-105. doi: 10.11648/j.iji.20170506.12

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AMA Style

Benson Olu Akinshipe, Friday Alfred Ehiaghe, Anthony Chukwuka Nwaobi, Emmanuel Babatunde Adedeji, Herbert Obi Okpala. The Patterns of Interferon-Gamma and Interleukin-10 Production as a Potential Immunological Biomarker for the Outcome of Mycobacterium Tuberculosis Infection. Int J Immunol. 2018;5(6):97-105. doi: 10.11648/j.iji.20170506.12

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@article{10.11648/j.iji.20170506.12,
  author = {Benson Olu Akinshipe and Friday Alfred Ehiaghe and Anthony Chukwuka Nwaobi and Emmanuel Babatunde Adedeji and Herbert Obi Okpala},
  title = {The Patterns of Interferon-Gamma and Interleukin-10 Production as a Potential Immunological Biomarker for the Outcome of Mycobacterium Tuberculosis Infection},
  journal = {International Journal of Immunology},
  volume = {5},
  number = {6},
  pages = {97-105},
  doi = {10.11648/j.iji.20170506.12},
  url = {https://doi.org/10.11648/j.iji.20170506.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.iji.20170506.12},
  abstract = {Deficiencies in current tuberculosis (TB) immunodiagnostics pipeline demand new approaches to control TB. Because the balance in key pro- and anti-inflammatory cytokines production could determine Mycobacterium Tuberculosis (MTb) infection outcome, this study aimed to determine the patterns of MTb-specific antigen-stimulated Interferon-gamma (IFN-y) and Interleukin-10 (IL-10) production in different clinical forms of MTb infection and to evaluate their concomitant changes during anti-TB treatment (ATT). Overall, 84 BCG-vaccinated HIV-negative adults, consisting of 25 Healthy Community Controls (HCC), 27 Latent Tuberculosis Infection (LTBI) cases, and a cohort of 32 Acute Pulmonary Tuberculosis (APTB) patients were investigated for IFN-y and IL-10 responses at enrollment (base-line) and during ATT at 2-month (ATT1) and 6-month (ATT2). At enrollment, groups didn’t differ significantly in age, gender, or CD4+ T counts but differed in the other socio-demographics, and hematological parameters, p<0.05. Base-line Sandwich ELISA – measured IFN-y responses were significantly higher in HCC (223.50±58.11pg/ml) compared with LTBI (128.82±41.81pg/ml) and APTB (47.82±22.05pg/ml), p<0.0001 in each case. During treatment, IFN-y levels increased significantly at ATT1 (125.37±16.09pg/ml) and ATT2 (203.35±23.24pg/ml), p<0.0001. Conversely, base-line IL-10 responses increased significantly in APTB (17.53±6.30pg/ml), compared with LTBI (10.71±2.39pg/ml) and HCC (7.49±2.02pg/ml), P<0.0001, but declined significantly at ATT1 (10.54±2.25pg/ml) and ATT2 (5.25±1.45pg/ml), P=<0.0001. Cytokines response combination ratio showed: ‘High’ HCC, ‘Intermediate’ LTBI, or ‘Low’ APTB ratio that increased during successful ATT; the two identified MDR-TB patients recorded fluctuating but constantly low ratio during ATT. These results demonstrate the immunocompetence of MTb-exposed adults, and that IFN-y and IL-10 cytokines cross-regulate, and strongly suggest a shift toward IFN-y-mediated pro-inflammatory host immune phenotype during effective control of MTb infection. The IFN-y/IL-10 response ratio is a novel potential immunological biomarker to assess if MTb infection is going to resolve, result in latency, progress to TB; or become drug-resistant.},
 year = {2018}
}

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TY  - JOUR
T1  - The Patterns of Interferon-Gamma and Interleukin-10 Production as a Potential Immunological Biomarker for the Outcome of Mycobacterium Tuberculosis Infection
AU  - Benson Olu Akinshipe
AU  - Friday Alfred Ehiaghe
AU  - Anthony Chukwuka Nwaobi
AU  - Emmanuel Babatunde Adedeji
AU  - Herbert Obi Okpala
Y1  - 2018/01/16
PY  - 2018
N1  - https://doi.org/10.11648/j.iji.20170506.12
DO  - 10.11648/j.iji.20170506.12
T2  - International Journal of Immunology
JF  - International Journal of Immunology
JO  - International Journal of Immunology
SP  - 97
EP  - 105
PB  - Science Publishing Group
SN  - 2329-1753
UR  - https://doi.org/10.11648/j.iji.20170506.12
AB  - Deficiencies in current tuberculosis (TB) immunodiagnostics pipeline demand new approaches to control TB. Because the balance in key pro- and anti-inflammatory cytokines production could determine Mycobacterium Tuberculosis (MTb) infection outcome, this study aimed to determine the patterns of MTb-specific antigen-stimulated Interferon-gamma (IFN-y) and Interleukin-10 (IL-10) production in different clinical forms of MTb infection and to evaluate their concomitant changes during anti-TB treatment (ATT). Overall, 84 BCG-vaccinated HIV-negative adults, consisting of 25 Healthy Community Controls (HCC), 27 Latent Tuberculosis Infection (LTBI) cases, and a cohort of 32 Acute Pulmonary Tuberculosis (APTB) patients were investigated for IFN-y and IL-10 responses at enrollment (base-line) and during ATT at 2-month (ATT1) and 6-month (ATT2). At enrollment, groups didn’t differ significantly in age, gender, or CD4+ T counts but differed in the other socio-demographics, and hematological parameters, p<0.05. Base-line Sandwich ELISA – measured IFN-y responses were significantly higher in HCC (223.50±58.11pg/ml) compared with LTBI (128.82±41.81pg/ml) and APTB (47.82±22.05pg/ml), p<0.0001 in each case. During treatment, IFN-y levels increased significantly at ATT1 (125.37±16.09pg/ml) and ATT2 (203.35±23.24pg/ml), p<0.0001. Conversely, base-line IL-10 responses increased significantly in APTB (17.53±6.30pg/ml), compared with LTBI (10.71±2.39pg/ml) and HCC (7.49±2.02pg/ml), P<0.0001, but declined significantly at ATT1 (10.54±2.25pg/ml) and ATT2 (5.25±1.45pg/ml), P=<0.0001. Cytokines response combination ratio showed: ‘High’ HCC, ‘Intermediate’ LTBI, or ‘Low’ APTB ratio that increased during successful ATT; the two identified MDR-TB patients recorded fluctuating but constantly low ratio during ATT. These results demonstrate the immunocompetence of MTb-exposed adults, and that IFN-y and IL-10 cytokines cross-regulate, and strongly suggest a shift toward IFN-y-mediated pro-inflammatory host immune phenotype during effective control of MTb infection. The IFN-y/IL-10 response ratio is a novel potential immunological biomarker to assess if MTb infection is going to resolve, result in latency, progress to TB; or become drug-resistant.
VL  - 5
IS  - 6
ER  -

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