Skip to main content
SpringerLink
Log in

Cytokine Polarization in Miliary and Pleural Tuberculosis

  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Cytokines were measured in patients with pleural effusion and miliary tuberculosis (TB). Patients with pleural effusion had significantly higher interferon-gamma (IFN-γ) levels (P < 0.001) in their pleural fluid as compared to that of peripheral blood of the same patients, thus exhibiting localization of predominantly Th1-type immunity in the pleural fluid. On the contrary, patients with miliary TB had higher IFN-γ levels in the peripheral blood as compared to their bronchoalveolar lavage fluid. Moreover, the median IFN-γ : IL-4 ratio in the peripheral blood of miliary TB patients was two-fold higher as compared to bronchoalveolar lavage fluid, suggesting that the cytokine profile at the disease site is skewed toward a Th2-like bias. Further, flow cytometry data revealed a significantly higher (P < 0.001) percentage of CD4+ pleural fluid lymphocytes expressing IFN-γ, whereas in the miliary TB, a nine-fold higher percentage of lymphocytes in bronchoalveolar lavage fluid expressed IL-4 in comparison with their peripheral CD4 T cells. Our data indicate, respectively, a Th1-like and Th2-like response in tuberculous pleural effusion and miliary TB, suggesting that these clinical forms of extrapulmonary tuberculosis probably reflect the extreme ends of a Th1–Th2 spectrum of the disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. World Health Organization: Global Tuberculosis Control. WHO Report 2001. Geneva, Switzerland, WHO/CDS/TB/2001.287

  2. Lucey DR, Clerici M, Shearer GM: Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic and inflammatory diseases. Clin Microbiol Rev 9:532–562, 1996

    Google Scholar 

  3. Yamamuro M, Uyemura K, Deans RJ, Weinberg K, Rea TH, Bloom BR, Modlin RL: Defining protective responses to pathogens: Cytokine profiles in leprosy lesions. Science 254:277–279, 1991

    Google Scholar 

  4. Snider DE, Onorato M: Epidemiology. In Tuberculosis: Clinical Management and New Challenges, MD Rossman, RR MacGregor (eds). New York, McGraw-Hill, 1995, pp 3–17

    Google Scholar 

  5. Surcel HM, Troye-Blomberg M, Paulie S, Andersson G, Moreno C, Pasvol G, Ivanyi J: Th1/Th2 profiles in tuberculosis based on the proliferation and cytokine response of blood lymphocytes to mycobacterial antigens. Immunology 81:171–176, 1994

    Google Scholar 

  6. Zhang M, Lin Y, Iyer DV, Gong J, Abrams JS, Barnes PF: T-cell cytokine responses in human infection with M. tuberculosis. Infect Immun 63:3231–3234, 1995

    Google Scholar 

  7. Sanchez FO, Rodriguez JI, Agudelo G, Garcia LF: Immune responsiveness and lymphokine production in patients with tuberculosis and healthy controls. Infect Immun 62:5673–5678, 1994

    Google Scholar 

  8. Lin Y, Zhang M, Hofman FM, Gong J, Barnes PF: Absence of a prominent Th2 cytokine response in human tuberculosis. Infect Immun 64:1351–1356, 1996

    Google Scholar 

  9. Ottenhoff THM, Kumararatne D, Casanova JL: Novel human immunodeficiencies reveal the essential role of type-1 cytokines in immunity to intracellular bacteria. Immunol Today 19:491–494, 1998

    Google Scholar 

  10. Flynn JL, Chan J, Triebold KJ, Dalton DK, Stewart TA, Bloom BR: An essential role for interferon gamma in resistance to Mycobacterium tuberculosis infection. J Exp Med 178:2249–2254, 1993

    Google Scholar 

  11. Hernandez Pando R, Orozcoe H, Sampieri A, Pavon L, Velasquillo C, Larriva-Sahd J, Alcocer JM, Madrid MV: Correlation between the kinetics of Th1/Th2 cells and pathology in a murine model of experimental pulmonary tuberculosis. Immunology 89:26–33, 1996

    Google Scholar 

  12. Lukacs NW, Addison CL, Gauldie J, Graham F, Simpson K, Strieter RM, Warmington K, Chensue SW, Kunkel SL: Transgeneinduced production of IL-4 alters the development and collagen expression of T helper cell I-type pulmonary granulomas. J Immunol 158:4478–4484, 1997

    Google Scholar 

  13. Sharma SK, Mohan A, Pande JN, Prasad L, Gupta AK, Khilnani, GC. Clinical profile, laboratory characteristics and outcome in miliary tuberculosis. QJM 88:29–37, 1995

    Google Scholar 

  14. Sharma SK, Saha PK, Dixit Y, Siddaramaiah NH, Seth P, Pande JN: HIV Seropositivity among adult tuberculosis patients in Delhi. Indian J Chest Dis Allied Sci 42:157–160, 2000

    Google Scholar 

  15. Sharma SK, Pande JN, Singh YN, Verma K, Kathait SS, Khare S, Malaviya AN: Pulmonary function and immunological abnormalities in miliary tuberculosis. Am Rev Respir Dis 145:1167–1171, 1992

    Google Scholar 

  16. Mitra DK, De Rosa SC, Luke A, Balamurugan A, Khaitan BK, Tung J, Mehra NK, Terr AI, O'Garra A, Herzenberg LA, Roederer M: Differential representations of memory T cell subsets are characteristic of polarized immunity in leprosy and atopic diseases. Int Immunol 11:1801–1810, 1999

    Google Scholar 

  17. Murphy KM, Ouyang W, Farrar JD, Yang J, Ranganath S, Asnagli H, Afkarian M, Murphy TL: Signaling and transcription in T helper development. Annu Rev Immunol 18:451–494, 2000

    Google Scholar 

  18. Yamada Y, Nakamura A, Hosoda M, Kato T, Asano T, Tonegawa K, Itoh M: Cytokines in pleural liquid for diagnosis of tuberculous pleurisy. Respir Med 95:577–581, 2001

    Google Scholar 

  19. Villegas MV, Labrada LA, Saravia NG: Evaluation of polymerase chain reaction, adenosine deaminase and interferon-gamma in pleural fluid for the differential diagnosis of pleural tuberculosis. Chest 118:1355–1364, 2000

    Google Scholar 

  20. Gerosa F, Nisii C, Righetti S, Micciolo R, Marchesini M, Cazzadori A, Trinchieri G: CD4(+) T cell clones producing both interferon-gamma and interleukin-10 predominate in bronchoalveolar lavages of active pulmonary tuberculosis patients. Clin Immunol 92:224–234, 1999

    Google Scholar 

  21. Condos R, Rom WN, Liu YM, Schluger NW: Local immune responses correlate with presentation and outcome in tuberculosis. Am J Respir Crit Care Med 157:729–735, 1998

    Google Scholar 

  22. Taha RA, Kotsimbos TC, Song YL, Menzies D, Hamid Q: IFN-gamma and IL-12 are increased in active compared with inactive tuberculosis. Am J Respir Crit Care Med 155:1135–1139, 1997

    Google Scholar 

  23. Somoskovi A, Zissel G, Zipfel PF, Ziegenhagen MW, Klaucke J, Haas H, Schlaak M, Muller-Quernheim J: Different cytokine patterns correlate with the extension of disease in pulmonary tuberculosis. Eur Cytokine Netw 10:135–142, 1999

    Google Scholar 

  24. Marchant A, Amedei A, Aszzurri A, Vekemans J, Benagiano M, Tamburini C, Lienhardt C, Corrah T, McAdam KP, Romagnani S, D'Elios MM, DelPrete G: Polarization of PPD-specific T-cell response of patients with tuberculosis from Th0 to Th1 profile after successful antimycobacterial therapy or in vitro conditioning with interferon-alpha or interleukin-12. Am J Respir Cell Mol Biol 24:187–194, 2001

    Google Scholar 

  25. Dlugovitzky D, Torres-Morales A, Rateni L, Farroni MA, Largacha C, Molteni O, Bottasso O: Circulating profile of Th1 and Th2 cytokines in tuberculosis patients with different degrees of pulmonary involvement. FEMS Immunol Med Microbiol 18:203–207, 1997

    Google Scholar 

  26. Baliko Z, Szereday L, Szekeres-Bartho J: Th2 biased immune response in cases with active Mycobacterium tuberculosis infection and tuberculin anergy. FEMS Immunol Med Microbiol 22:199–204, 1998

    Google Scholar 

  27. Seah GT, Scott GM, Rook GAW: Type 2 cytokine gene activation and its relationship to extent of disease in patients with tuberculosis. J Infect Dis 181:385–389, 2000

    Google Scholar 

  28. van Crevel R, Karyadi E, Preyers F, Leenders M, Kullberg BJ, Nelwan RH, van der Meer JW: Increased production of interleukin 4 by CD4 and CD8 T cells from patients with tuberculosis is related to the presence of pulmonary cavities. J Infect Dis 181: 1194–1197, 2000

    Google Scholar 

  29. Atamas SP, Choi J, Yurovsky VV, White B: An alternative splice variant of human IL-4. IL-4 delta 2 inhibits IL-4-stimulated T-cell proliferation. J Immunol 156:435–441, 1996

    Google Scholar 

  30. Jung NGT, Schauer U, Heusser C, Neumann C, Rieger C: Detection of intracellular cytokines by flow cytometry. J Immunol Methods 159:197–207, 1993

    Google Scholar 

  31. Mossman TR, Moore KW: The role of IL-10 in cross-regulation of TH1 and TH2 Responses. Immunol Today 12:A49–53, 1991

    Google Scholar 

  32. DiPiro JT: Cytokine networks with infection: Mycobacterial infections, leishmaniasis, human immunodeficiency virus infection, and sepsis. Pharmacotherapy 17:205–223, 1997

    Google Scholar 

  33. Adams JF, Scholvinck EH, Gie RP, Potter PC, Beyers N, Beyers AD: Decline in total serum IgE after treatment for tuberculosis. Lancet 353:2030–2033, 1999

    Google Scholar 

  34. Sieling PA, Modlin RL: Cytokine patterns at the site of mycobacterial infection. Immunobiology 191:378–387, 1994

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, All, India Institute of Medical Sciences, New Delhi-110 029, India

    Surendra K. Sharma

  2. Department of Transplant Immunology and Immunogenetics, All, India Institute of Medical Sciences, New Delhi-110 029, India

    Dipender K. Mitra, Arumugam Balamurugan & Narinder K. Mehra

  3. Department of Biostatistics, All, India Institute of Medical Sciences, New Delhi-110 029, India

    Ravindra M. Pandey

Authors
  1. Surendra K. Sharma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dipender K. Mitra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Arumugam Balamurugan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ravindra M. Pandey
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Narinder K. Mehra
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sharma, S.K., Mitra, D.K., Balamurugan, A. et al. Cytokine Polarization in Miliary and Pleural Tuberculosis. J Clin Immunol 22, 345–352 (2002). https://doi.org/10.1023/A:1020604331886

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1020604331886

Search

Navigation