Skip to main content
PMC home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 2003 Feb;12(1):9–14. doi: 10.1080/0962935031000096926

Correlation of serum tumor necrosis factor-alpha, interleukin-4 and soluble interleukin-2 receptor levels with radiologic and clinical manifestations in active pulmonary tuberculosis.

Levent Kart 1, Hakan Buyukoglan 1, Ishak O Tekin 1, Remzi Altin 1, Zuhal Senturk 1, Inci Gulmez 1, Ramazan Demir 1, Mustafa Ozesmi 1
PMCID: PMC1781590  PMID: 12745543

Abstract

The precise clinical manifestations of tuberculosis are likely to result from a complex interaction between the host and the pathogen. We took serum samples from a group of patients with a variety of clinical and radiological stages of pulmonary tuberculosis in order to characterize tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4) and soluble interleukin-2 receptor (sIL-2R) response. We further evaluated whether the levels of TNF-alpha, IL-4 and soluble IL-2R are related with each other, and also evaluated the levels of TNF-alpha, IL-4 and sIL-2R after anti-tuberculosis therapy and relation with radiologic scores. Forty-three inpatients with active pulmonary tuberculosis and 19 healthy controls participated in the study. Patients were divided into four categories radiologically on chest X-ray (minimal, moderate-advanced, far-advanced and with miliary infiltration). Concentrations of TNF-alpha (20.9+/-10/15.4+/-8 pg/ml) and sIL-2R (2569+/-842/1444+/-514 pg/ml) were statistically different between patients and controls (p=0.02 and p=0.0001, respectively). Before chemotherapy there was a positive correlation between TNF-alpha and sIL-2R (r=0.34), but there was no correlation between IL-4 and TNF-alpha, and between IL-4 and sIL-2R (r=-0.23 and r=-0.22). The TNF-alpha level was not statistically different in four groups before and after chemotherapy. Results of this study provided some evidence confirming the previously reported role of TNF-alpha, IL-4 and sIL 2R in the control of tuberculosis, but these cytokines were not found related with disease severity.

Full Text

The Full Text of this article is available as a PDF (104.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abe Y., Nakamura M., Oshika Y., Hatanaka H., Tokunaga T., Ohkubo Y., Hashizume T., Suzuki K., Fujino T. Serum levels of vascular endothelial growth factor and cavity formation in active pulmonary tuberculosis. Respiration. 2001;68(5):496–500. doi: 10.1159/000050557. [DOI] [PubMed] [Google Scholar]
  2. Algren J. T., Lal S., Cutliff S. A., Richman B. J. Predictors of outcome in acute meningococcal infection in children. Crit Care Med. 1993 Mar;21(3):447–452. doi: 10.1097/00003246-199303000-00024. [DOI] [PubMed] [Google Scholar]
  3. Barnes P. F., Fong S. J., Brennan P. J., Twomey P. E., Mazumder A., Modlin R. L. Local production of tumor necrosis factor and IFN-gamma in tuberculous pleuritis. J Immunol. 1990 Jul 1;145(1):149–154. [PubMed] [Google Scholar]
  4. Bergeron A., Bonay M., Kambouchner M., Lecossier D., Riquet M., Soler P., Hance A., Tazi A. Cytokine patterns in tuberculous and sarcoid granulomas: correlations with histopathologic features of the granulomatous response. J Immunol. 1997 Sep 15;159(6):3034–3043. [PubMed] [Google Scholar]
  5. Bermudez L. E., Kaplan G. Recombinant cytokines for controlling mycobacterial infections. Trends Microbiol. 1995 Jan;3(1):22–27. doi: 10.1016/s0966-842x(00)88864-2. [DOI] [PubMed] [Google Scholar]
  6. Bermudez L. E., Young L. S. Tumor necrosis factor, alone or in combination with IL-2, but not IFN-gamma, is associated with macrophage killing of Mycobacterium avium complex. J Immunol. 1988 May 1;140(9):3006–3013. [PubMed] [Google Scholar]
  7. Casarini M., Ameglio F., Alemanno L., Zangrilli P., Mattia P., Paone G., Bisetti A., Giosuè S. Cytokine levels correlate with a radiologic score in active pulmonary tuberculosis. Am J Respir Crit Care Med. 1999 Jan;159(1):143–148. doi: 10.1164/ajrccm.159.1.9803066. [DOI] [PubMed] [Google Scholar]
  8. Dinarello C. A. Proinflammatory cytokines. Chest. 2000 Aug;118(2):503–508. doi: 10.1378/chest.118.2.503. [DOI] [PubMed] [Google Scholar]
  9. Dlugovitzky D., Torres-Morales A., Rateni L., Farroni M. A., 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. 1997 Jul;18(3):203–207. doi: 10.1111/j.1574-695X.1997.tb01046.x. [DOI] [PubMed] [Google Scholar]
  10. Flynn J. L., Goldstein M. M., Triebold K. J., Koller B., Bloom B. R. Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):12013–12017. doi: 10.1073/pnas.89.24.12013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Foley N., Lambert C., McNicol M., Johnson N., Rook G. A. An inhibitor of the toxicity of tumour necrosis factor in the serum of patients with sarcoidosis, tuberculosis and Crohn's disease. Clin Exp Immunol. 1990 Jun;80(3):395–399. doi: 10.1111/j.1365-2249.1990.tb03299.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Furney S. K., Skinner P. S., Roberts A. D., Appelberg R., Orme I. M. Capacity of Mycobacterium avium isolates to grow well or poorly in murine macrophages resides in their ability to induce secretion of tumor necrosis factor. Infect Immun. 1992 Oct;60(10):4410–4413. doi: 10.1128/iai.60.10.4410-4413.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kaplan G., Freedman V. H. The role of cytokines in the immune response to tuberculosis. Res Immunol. 1996 Oct-Dec;147(8-9):565–572. doi: 10.1016/s0923-2494(97)85223-6. [DOI] [PubMed] [Google Scholar]
  14. Kelley J. Cytokines of the lung. Am Rev Respir Dis. 1990 Mar;141(3):765–788. doi: 10.1164/ajrccm/141.3.765. [DOI] [PubMed] [Google Scholar]
  15. Kindler V., Sappino A. P., Grau G. E., Piguet P. F., Vassalli P. The inducing role of tumor necrosis factor in the development of bactericidal granulomas during BCG infection. Cell. 1989 Mar 10;56(5):731–740. doi: 10.1016/0092-8674(89)90676-4. [DOI] [PubMed] [Google Scholar]
  16. Kobayashi K., Kaneda K., Kasama T. Immunopathogenesis of delayed-type hypersensitivity. Microsc Res Tech. 2001 May 15;53(4):241–245. doi: 10.1002/jemt.1090. [DOI] [PubMed] [Google Scholar]
  17. Lin Y., Zhang M., Hofman F. M., Gong J., Barnes P. F. Absence of a prominent Th2 cytokine response in human tuberculosis. Infect Immun. 1996 Apr;64(4):1351–1356. doi: 10.1128/iai.64.4.1351-1356.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Orme I. M., Roberts A. D., Griffin J. P., Abrams J. S. Cytokine secretion by CD4 T lymphocytes acquired in response to Mycobacterium tuberculosis infection. J Immunol. 1993 Jul 1;151(1):518–525. [PubMed] [Google Scholar]
  19. Orme I. M. The kinetics of emergence and loss of mediator T lymphocytes acquired in response to infection with Mycobacterium tuberculosis. J Immunol. 1987 Jan 1;138(1):293–298. [PubMed] [Google Scholar]
  20. Ribeiro-Rodrigues Rodrigo, Resende Co Tatiana, Johnson John L., Ribeiro Fabiola, Palaci Moises, Sá Ricardo T., Maciel Ethel L., Pereira Lima Fausto E., Dettoni Valderio, Toossi Zahra. Sputum cytokine levels in patients with pulmonary tuberculosis as early markers of mycobacterial clearance. Clin Diagn Lab Immunol. 2002 Jul;9(4):818–823. doi: 10.1128/CDLI.9.4.818-823.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Seah G. T., Scott G. M., Rook G. A. Type 2 cytokine gene activation and its relationship to extent of disease in patients with tuberculosis. J Infect Dis. 2000 Jan;181(1):385–389. doi: 10.1086/315200. [DOI] [PubMed] [Google Scholar]
  22. Serbina N. V., Flynn J. L. Early emergence of CD8(+) T cells primed for production of type 1 cytokines in the lungs of Mycobacterium tuberculosis-infected mice. Infect Immun. 1999 Aug;67(8):3980–3988. doi: 10.1128/iai.67.8.3980-3988.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sodhi A., Gong J., Silva C., Qian D., Barnes P. F. Clinical correlates of interferon gamma production in patients with tuberculosis. Clin Infect Dis. 1997 Sep;25(3):617–620. doi: 10.1086/513769. [DOI] [PubMed] [Google Scholar]
  24. Surcel H. M., 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. 1994 Feb;81(2):171–176. [PMC free article] [PubMed] [Google Scholar]
  25. Takahashi S., Setoguchi Y., Nukiwa T., Kira S. Soluble interleukin-2 receptor in sera of patients with pulmonary tuberculosis. Chest. 1991 Feb;99(2):310–314. doi: 10.1378/chest.99.2.310. [DOI] [PubMed] [Google Scholar]
  26. Takashima T., Ueta C., Tsuyuguchi I., Kishimoto S. Production of tumor necrosis factor alpha by monocytes from patients with pulmonary tuberculosis. Infect Immun. 1990 Oct;58(10):3286–3292. doi: 10.1128/iai.58.10.3286-3292.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Toossi Z., Ellner J. J. The role of TGF beta in the pathogenesis of human tuberculosis. Clin Immunol Immunopathol. 1998 May;87(2):107–114. doi: 10.1006/clin.1998.4528. [DOI] [PubMed] [Google Scholar]
  28. Torres M., Herrera T., Villareal H., Rich E. A., Sada E. Cytokine profiles for peripheral blood lymphocytes from patients with active pulmonary tuberculosis and healthy household contacts in response to the 30-kilodalton antigen of Mycobacterium tuberculosis. Infect Immun. 1998 Jan;66(1):176–180. doi: 10.1128/iai.66.1.176-180.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tsao T. C., Hong J. h., Li L. F., Hsieh M. J., Liao S. K., Chang K. S. Imbalances between tumor necrosis factor-alpha and its soluble receptor forms, and interleukin-1beta and interleukin-1 receptor antagonist in BAL fluid of cavitary pulmonary tuberculosis. Chest. 2000 Jan;117(1):103–109. doi: 10.1378/chest.117.1.103. [DOI] [PubMed] [Google Scholar]
  30. Turner J., D'Souza C. D., Pearl J. E., Marietta P., Noel M., Frank A. A., Appelberg R., Orme I. M., Cooper A. M. CD8- and CD95/95L-dependent mechanisms of resistance in mice with chronic pulmonary tuberculosis. Am J Respir Cell Mol Biol. 2001 Feb;24(2):203–209. doi: 10.1165/ajrcmb.24.2.4370. [DOI] [PubMed] [Google Scholar]
  31. Turner J., Dockrell H. M. Stimulation of human peripheral blood mononuclear cells with live Mycobacterium bovis BCG activates cytolytic CD8+ T cells in vitro. Immunology. 1996 Mar;87(3):339–342. doi: 10.1046/j.1365-2567.1996.512590.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wallis R. S., Ellner J. J. Cytokines and tuberculosis. J Leukoc Biol. 1994 May;55(5):676–681. doi: 10.1002/jlb.55.5.676. [DOI] [PubMed] [Google Scholar]
  33. Yamamura M., Uyemura K., Deans R. J., Weinberg K., Rea T. H., Bloom B. R., Modlin R. L. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science. 1991 Oct 11;254(5029):277–279. doi: 10.1126/science.254.5029.277. [DOI] [PubMed] [Google Scholar]
  34. Yamamura Y. [Activated macrophages and cytotoxicity]. Kekkaku. 1989 Oct;64(10):679–681. [PubMed] [Google Scholar]
  35. Zhang M., Lin Y., Iyer D. V., Gong J., Abrams J. S., Barnes P. F. T-cell cytokine responses in human infection with Mycobacterium tuberculosis. Infect Immun. 1995 Aug;63(8):3231–3234. doi: 10.1128/iai.63.8.3231-3234.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. van Crevel R., Karyadi E., Preyers F., Leenders M., Kullberg B. J., Nelwan R. H., van der Meer J. W. 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. 2000 Mar;181(3):1194–1197. doi: 10.1086/315325. [DOI] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES