Tuberc Respir Dis.  2009 Mar;66(3):205-210. 10.4046/trd.2009.66.3.205.

Preliminary Study for Elevated Serum CXCL10 and CXCL11 in Active Pulmonary Tuberculosis Compared with the Other Pulmonary Diseases

• Park MY
• Kim SY
• Hwang SH
• Kim JE
• Lee MK
• Lee CH
• Lee EY

• KMID: 1846381
• DOI: http://doi.org/10.4046/trd.2009.66.3.205

Abstract

BACKGROUND: CXCL10 and CXCL11, which are family of CXCR3 ligands, are expressed by lymphocytes and even by bronchial epithelial cells if the cellular immunity is activated. This study evaluated the potential utility of CXCL10 and CXCL11 in the serum for active pulmonary tuberculosis in comparison with lung cancer, which activates the cellular immunity, and benign lung diseases.
METHODS
Patients who newly visited Pusan National University Hospital from January 2007 to December 2007 and were suspected of having lung cancer or tuberculosis were enrolled prospectively. The patients were classified pathologically and clinically into three groups, 47 with lung cancer, 18 with active pulmonary tuberculosis and 38 control patients with benign pulmonary disease. ELISA was used to determine the levels of CXCL10 and CXCL11 were determined in the serum.
RESULTS
The level of CXCL10 and CXCL11 were significantly higher in the active pulmonary tuberculosis group than in the lung cancer and benign lung disease groups (p<0.001, Kruskal-Wallis). The level of CXCL11 was significantly higher in the lung cancer group than in the benign pulmonary disease group, but there was no significant difference in level of CXCL10 between the three groups (p<0.001, p=0.655, respectively, Mann-Whitney U). The level of CXCL10 in patients with stage III+IV lung cancer was significantly higher than those with stage I+II, but there was no significant difference in the level of CXCL11 between the groups (p<0.001, p=0.07, respectively, Mann-Whitney U). There was no significant difference in the level of CXCL10 and CXCL11 between those with the presence and absence of lung cancer metastasis. There was a significant correlation between the level of CXCL10 and CXCL11 (r=0.223, p<0.001).
CONCLUSION
CXCL10 and CXCL11 may be a potential useful markers for active pulmonary tuberculosis if used alongside other diagnostic methods.

Keyword

Active pulmonary tuberculosis; Lung neoplasms; CXCL10; CXCL11

MeSH Terms

Enzyme-Linked Immunosorbent Assay
Epithelial Cells
Humans
Immunity, Cellular
Ligands
Lung Diseases
Lung Neoplasms
Lymphocytes
Neoplasm Metastasis
Prospective Studies
Tuberculosis
Tuberculosis, Pulmonary
Ligands

Figure

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  Figure 1 The serum concentration of CXCL10 (pg/mL) in lung cancer patients, active pulmonary tuberculosis patients and benign pulmonary disease controls.

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  Figure 2 The serum concentration of CXCL11 (pg/mL) in lung cancer patients, active pulmonary tuberculosis patients and benign pulmonary disease controls.

Reference

1. Strieter RM, Belperio JA, Burdick MD, Sharma S, Dubinett SM, Keane MP. CXC chemokines: angiogenesis, immunoangiostasis, and metastases in lung cancer. Ann N Y Acad Sci. 2004. 1028:351–360.

2. Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity. 2000. 12:121–127.

3. Murphy PM. International Union of Pharmacology. XXX. Update on chemokine receptor nomenclature. Pharmacol Rev. 2002. 54:227–229.

4. Murphy PM, Baggiolini M, Charo IF, Hébert CA, Horuk R, Matsushima K, et al. International Union of Pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev. 2000. 52:145–176.

5. Mantovani A. The chemokine system: redundancy for robust outputs. Immunol Today. 1999. 20:254–257.

6. Luster AD. The role of chemokines in linking innate and adaptive immunity. Curr Opin Immunol. 2002. 14:129–135.

7. Yang J, Richmond A. The angiostatic activity of interferon-inducible protein-10/CXCL10 in human melanoma depends on binding to CXCR3 but not to glycosaminoglycan. Mol Ther. 2004. 9:846–855.

8. Cole KE, Strick CA, Paradis TJ, Ogborne KT, Loetscher M, Gladue RP, et al. Interferon-inducible T cell alpha chemoattractant (I-TAC): a novel non-ELR CXC chemokine with potent activity on activated T cells through selective high affinity binding to CXCR3. J Exp Med. 1998. 187:2009–2021.

9. Méndez-Samperio P. Expression and regulation of chemokines in mycobacterial infection. J Infect. 2008. 57:374–384.

10. Lee JS, Lee JY, Choi HH, Son JW, Kim KH, Paik TH, et al. Elevated levels of interferon-inducible protein-10 (IP)-10/CXCL10, but not of interferon-gamma, in patients with pulmonary tuberculosis. J Bacteriol Virol. 2007. 37:137–146.

11. Sauty A, Dziejman M, Taha RA, Iarossi AS, Neote K, Garcia-Zepeda EA, et al. The T cell-specific CXC chemokines IP-10, Mig, and I-TAC are expressed by activated human bronchial epithelial cells. J Immunol. 1999. 162:3549–3558.

12. Ruhwald M, Petersen J, Kofoed K, Nakaoka H, Cuevas LE, Lawson L, et al. Improving T-cell assays for the diagnosis of latent TB infection: potential of a diagnostic test based on IP-10. PLoS ONE. 2008. 3:e2858.

13. Supriya P, Chandrasekaran P, Das SD. Diagnostic utility of interferon-gamma-induced protein of 10 kDa (IP-10) in tuberculous pleurisy. Diagn Microbiol Infect Dis. 2008. 62:186–192.

14. Yang CS, Lee JS, Lee HM, Shim TS, Son JW, Jung SS, et al. Differential cytokine levels and immunoreactivities against Mycobacterium tuberculosis antigens between tuberculous and malignant effusions. Respir Med. 2008. 102:280–286.

15. Fenton MJ, Vermeulen MW. Immunopathology of tuberculosis: roles of macrophages and monocytes. Infect Immun. 1996. 64:683–690.

16. Boon T, Cerottini JC, Van den Eynde B, van der Bruggen P, Van Pel A. Tumor antigens recognized by T lymphocytes. Annu Rev Immunol. 1994. 12:337–365.

17. Kang YA, Lee HW, Hwang SS, Um SW, Han SK, Shim YS, et al. Usefulness of whole-blood interferon-gamma assay and interferon-gamma enzyme-linked immunospot assay in the diagnosis of active pulmonary tuberculosis. Chest. 2007. 132:959–965.

18. Walrath J, Zukowski L, Krywiak A, Silver RF. Resident Th1-like effector memory cells in pulmonary recall responses to Mycobacterium tuberculosis. Am J Respir Cell Mol Biol. 2005. 33:48–55.

19. Silver RF, Zukowski L, Kotake S, Li Q, Pozuelo F, Krywiak A, et al. Recruitment of antigen-specific Th1-like responses to the human lung following bronchoscopic segmental challenge with purified protein derivative of Mycobacterium tuberculosis. Am J Respir Cell Mol Biol. 2003. 29:117–123.

20. Maekawa S, Iwasaki A, Shirakusa T, Kawakami T, Yanagisawa J, Tanaka T, et al. Association between the expression of chemokine receptors CCR7 and CXCR3, and lymph node metastatic potential in lung adenocarcinoma. Oncol Rep. 2008. 19:1461–1468.

21. Goldberg-Bittman L, Sagi-Assif O, Meshel T, Nevo I, Levy-Nissenbaum O, Yron I, et al. Cellular characteristics of neuroblastoma cells: regulation by the ELR--CXC chemokine CXCL10 and expression of a CXCR3-like receptor. Cytokine. 2005. 29:105–117.

22. Jones D, Benjamin RJ, Shahsafaei A, Dorfman DM. The chemokine receptor CXCR3 is expressed in a subset of B-cell lymphomas and is a marker of B-cell chronic lymphocytic leukemia. Blood. 2000. 95:627–632.

23. Robledo MM, Bartolome RA, Longo N, Rodríguez-Frade JM, Mellado M, Longo I, et al. Expression of functional chemokine receptors CXCR3 and CXCR4 on human melanoma cells. J Biol Chem. 2001. 276:45098–45105.

24. Goldberg-Bittman L, Neumark E, Sagi-Assif O, Azenshtein E, Meshel T, Witz IP, et al. The expression of the chemokine receptor CXCR3 and its ligand, CXCL10, in human breast adenocarcinoma cell lines. Immunol Lett. 2004. 92:171–178.

25. Kawada K, Sonoshita M, Sakashita H, Takabayashi A, Yamaoka Y, Manabe T, et al. Pivotal role of CXCR3 in melanoma cell metastasis to lymph nodes. Cancer Res. 2004. 64:4010–4017.

26. Engl T, Relja B, Blumenberg C, Müller I, Ringel EM, Beecken WD, et al. Prostate tumor CXC-chemokine profile correlates with cell adhesion to endothelium and extracellular matrix. Life Sci. 2006. 78:1784–1793.

27. Singh S, Sadanandam A, Singh RK. Chemokines in tumor angiogenesis and metastasis. Cancer Metastasis Rev. 2007. 26:453–467.

28. Whittaker E, Gordon A, Kampmann B. Is IP-10 a better biomarker for active and latent tuberculosis in children than IFNgamma? PLoS ONE. 2008. 3:e3901.