Volume 5, Issue 6, December 2017, Page: 97-105
The Patterns of Interferon-Gamma and Interleukin-10 Production as a Potential Immunological Biomarker for the Outcome of Mycobacterium Tuberculosis Infection
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; Lahor Research Laboratory and Medical Centre, Benin City, 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
Received: Dec. 5, 2017;       Accepted: Dec. 13, 2017;       Published: Jan. 16, 2018
DOI: 10.11648/j.iji.20170506.12      View  2472      Downloads  203
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.
Adults, Mycobacterium Tuberculosis Infection, Immunodiagnostics, Cytokines Production Ratio, TB Control
To cite this article
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, International Journal of Immunology. Vol. 5, No. 6, 2017, pp. 97-105. doi: 10.11648/j.iji.20170506.12
Copyright © 2017 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
World Health Organization (WHO). Tuberculosis Report (2016.). http//www.who,int/mediacentre/factsheets/fs104/en/.
Espinal M A, Laszlo A, Simonsen L, Boulahbal F, Kim S. J, Reniero A. et al. Global Trends in Resistance to anti-tuberculosis drugs. World Health Organization-International Union against Tuberculosis and Lung Disease Working Group on Anti-tuberculosis Drug Resistance Surveillance. New Engl J Med 2001; 344: 1294-1303.
World Health Organization (WHO). Global Tuberculosis Report in 2014 (2015).
Collins H. L, Kaufmann S. H. E. Acquired immunity against bacteria. In: SHE Kaufmann, A Sher, R Ahmed (Eds.). Immunology of Infectious Diseases. ASM Press, Washington DC 2002. Pp 207-221. Chapter 15.
Schluger N. W. The pathogenesis of tuberculosis: the first one hundred (and twenty-three) years. Am. J. Respir Cell Mol. Biol. 2005; 32: 251-256.
Flynn J. L, Chan J. Immunology of Tuberculosis. Annual Review Immunol. 2001; 19: 93-129 [PubMed].
Diel R, Goletti D, Ferrara G, Bothamley C. et al. Interferon-gamma release assays for the diagnosis of latent mycobacterium tuberculosis infection: a systematic review and meta-analysis. Eur Respir J. 2011; 13: 88-99.
Pai M, Zwerling A, Menzies D. Systematic review: T-cells-based assays for the diagnosis of latent tuberculosis infection: an update. Ann Intern Med. 2008; 149: 177-184.
Golleti D, Petraccioli E, Joosten S. A, Ottenhoff T. H. M. Tuberculosis Biomarkers: From Diagnosis to Protection. Infect Dis Rep. 2016; 8 (2): 6568. PMCID: PMC 4927936.
{10} Tebrugge M, Dutta B, Donath S, Ritz N, Forbes B. et al. Mycobacteria-specific Cytokine Responses Detect Tuberculosis Infection and Distinguish Latent from Active Tuberculosis. Amer J Resp & Critic Care Med 2015; Vol 192: 4.
Redford P. S, Murray P. J, O’Garra A. The role of IL- 10 in immune regulation during M. tuberculosis infection. Mucosal Immunology. 2011; 4: 261-270.
Turner J, Gonzalez- Juarrero M, Ellis D. L, Basaraba R. J, Kipnis A. et al. In vivo IL-10 production reactivates chronic pulmonary Tuberculosis in C57BL/6 mice. J. Immunology 2002; 169 (11): 6343-6351 [PubMed].
Sester M, Sotgiu G, Lange C, Giehl C, Girardi E, Migliori G. B, Bossink A, Dheda K, Diel R, Dominguez J. et al. Interferon-γ release assays for the diagnosis of active tuberculosis: a systematic review and meta-analysis. Eur Respir J 2011; 37: 100–111.
Akinshipe B. O, Ezeani P. C, Digban K. A, Ehiaghe F. A, Adedeji E. B, Ehiaghe J. I. Immunodiagnostic Potential of an In-vitro Interferon-Gamma Release Assay for Latent Tuberculosis Infection among Apparently Healthy Individuals in Okada Community, Nigeria. Int J Immunol 2017, vol 5, No. 3; pp. 41-48.
Global Tuberculosis Control 2016, WHO, Geneva, 2016.www.who.int/tb/publication/global report/en/ Use of high burden country list for TB by WHO in post-2015 era.
Nigeria National Tuberculosis and Leprosy Control Program (NTBLCP), National Strategic Plan-TB 2015-2020.
Enarson D. E, Rieder H. L, Arnadottir T, Trebucq A. Management of Tuberculosis; a guide for low income countries. 5th edn. Paris: IUATLD; 2000.
Miri-Dashe T, Osewe S, Tokdung M, Daniel N, Choji R. P. et al. Comprehensive reference ranges for hematology and clinical chemistry parameters derived from normal Nigerian adults. PLoS One. 2014; 9 (5): 939.
Shafee M, Abbas F, Ashraf M, Mengal M. A, Kakar N, et al. Hematological profile and risk factors associated with pulmonary tuberculosis patients in Quetta, Pakistan. Pakistan J Med Sci. 2014; 30 (1): 36-40.
Adewole O. O, Ota M. O, Erhabor G. E, Owiafe P, Oladimeji A, Obaseki D. Interferon-gamma treatment kinetics among patients with active pulmonary tuberculosis. Niger Med J. 2013; 54 (6): 376-381.
Al-Attiyah R, Madi N. M, El-Shamy A. M, Wiker H. G, Andersen P, Mustafa A. S. Cytokine profiles in tuberculosis patients and healthy subjects in response to complex and single antigens of Mycobacterium Tuberculosis. Pathogens and Disease. 2006; 47 (2): 254-261.
Deveci F, Handan Akbulut H, Turgut T, Hamdi Muz M. Changes in serum cytokine levels in Active Tuberculosis with treatment. Mediators Inflamm. 2005; Oct 24; 2005 (5): 256-262.
Jeong Y. H, Lee H, Kim S, Cho J. E, Chang J, Sun Chang Shin S. J, Lee H, Kang Y. A, Cho S. N, Ha S. J. Discrimination between Active and Latent Tuberculosis Based on Ratio of Antigen-Specific to Mitogen-Induced IP-10 Production. J Clin Microbiol. 2015; 53: 504-510.
Lee J. S, Song C. H, Kim C. H, Kong S. J, Shon M. H, Kim H. J, Park J. k, Paik T. H, Jo E. K. Profiles of INF-y and its regulatory cytokines (IL-12, IL-18 and IL-10) in peripheral blood mononuclear cells from patients with multidrug-resistant tuberculosis. Clin Exp Immunol. 2002; 128 (3): 516-524.
Djoba Siawaya J. F, Beyers N, van Helden P, Walz G. Differential cytokine secretion and early response in patients with pulmonary tuberculosis. Clin Exp Immunol. 2009; 156 (1): 69-77.
Nemeth J, Winkler H. M, Boeck L, Adegnika A. A, Perkmann T, Ramharter M. et al. Increased specific T cell cytokine responses in patients with active pulmonary tuberculosis from Central Africa. Microbes Infect. 2005; 7: 1161-9. [PubMed].
Onwubalili J. K, Scott G. M, Robinson J. A. Deficient immune interferon production in tuberculosis. Clin Exp Immunol. 1985; 59: 405-413. [PMC free article] [PubMed].
Subronto, Y. W, Van Meijgaarden K. E, Geluk S, Arend S. M, Sunardi T, Franken K. L. et al. Interferon-gamma production in response to M. tuberculosis antigens in TB patients in Indonesia. Ad Exp Med Biol. 2003; 531: 249-260 [PubMed].
Bekker LG, Maartens G, Steyn L, Kaplan G. Selective increase in plasma tumor necrosis factor-alpha and concomitant clinical deterioration after initiating therapy in patients with severe Tuberculosis. J Infect Dis. 1998; 80: 161-9 [PubMed].
Demissie A, Abebe M, Aseffa A, Rook G, Fletcher H, Zumla A and the VACSEL Study Group. Healthy individuals that control a latent infection with mycobacterium Tuberculosis express high levels of Th1 cytokines and the IL-14 antagonist IL-4 delta 2. J Immunol 2004; 172: 6938-6943.
Verbon A, Juffermans N, Van Deventer S. J. H, Spleelman P, Van Deutekom H, Van Der Poll T. Serum concentrations of cytokines in patients with active tuberculosis (TB) and after treatment. Clin & Exp Immunol. 1999 Jan; 115 (1): 110-113.
Colditz GA, Brewer TF, Berkey CS, Mosteller F et al. Efficacy of BCG vaccine in the prevention of Tuberculosis Meta-analysis of the Published Literature. JAMA 1994; 271: 698-702.
Lago P. M., Boechat N, Migueis D. P, Almeida S. A, Lazarini C. L, Saldanha M. M, Kritski A. L, Ho J. L, Lapa e Silva J. R. Interleukin-10 and interferon-gamma patterns during tuberculosis treatment: possible association with recurrence. 2012; Int J Tuberc Lung Dis; 16 (5): 656-659.
Davies P D, Pai M. The Diagnosis and Misdiagnosis of Tuberculosis. Int J Tuberc Lung Dis. 2008; 12: 1226-34 [PubMed].
Browse journals by subject