Skip to main content
PMC home page
Thorax logoLink to Thorax
. 1990 Jul;45(7):536–540. doi: 10.1136/thx.45.7.536

Idiopathic pulmonary fibrosis: can cell mediated immunity markers predict clinical outcome?

R Meliconi 1, E Lalli 1, R M Borzì 1, C Sturani 1, V Galavotti 1, G Gunella 1, R Miniero 1, A Facchini 1, G Gasbarrini 1
PMCID: PMC462584  PMID: 2118691

Abstract

Most of the cells found in lung parenchyma in patients with idiopathic pulmonary fibrosis are activated T lymphocytes and macrophages. The serum levels of three markers of cell mediated immunity were measured in 20 patients with idiopathic pulmonary fibrosis, in 20 normal subjects and in 12 patients with sarcoidosis to evaluate their clinical and prognostic significance in idiopathic pulmonary fibrosis. The three markers were: soluble CD8 (from activated suppressor-cytotoxic lymphocytes), soluble interleukin (IL)-2 receptors (from activated T cells and macrophages), and neopterin (from activated macrophages). Patients with idiopathic pulmonary fibrosis had higher levels of all three markers than the control subjects. Soluble IL-2 receptor and neopterin tended to be lower (though not significantly) in patients with idiopathic pulmonary fibrosis than in those with sarcoidosis, whereas soluble CD8 was similar in the two groups of patients. No correlation was found between soluble IL-2 receptors or soluble CD8 and the clinical, radiological, and physiological measures of disease activity or with clinical outcome (after a mean follow up of 23 months). Tumour necrosis factor levels were also determined. Only 30% of patients with idiopathic pulmonary fibrosis or sarcoidosis had detectable circulating tumour necrosis factor; these patients had a lower percentage of bronchoalveolar lavage fluid neutrophils in their lavage fluid. Tumour necrosis factor levels did not correlate with clinical measures of severity or outcome. Thus our data support the hypothesis that cell mediated alveolitis occurs in idiopathic pulmonary fibrosis. They do not, however, provide evidence to support the use of these markers of cell mediated immunity to monitor the clinical course in these patients.

Full text

PDF
536

Selected References

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

  1. BLAKEMORE W. S., FORSTER R. E., MORTON J. W., OGILVIE C. M. A standardized breath holding technique for the clinical measurement of the diffusing capacity of the lung for carbon monoxide. J Clin Invest. 1957 Jan;36(1 Pt 1):1–17. doi: 10.1172/JCI103402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Balderas R. S., Josimovic-Alasevic O., Diamantstein T., Dixon F. J., Theofilopoulos A. N. Elevated titers of cell-free interleukin 2 receptor in serum of lupus mice. J Immunol. 1987 Sep 1;139(5):1496–1500. [PubMed] [Google Scholar]
  3. Beutler B., Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med. 1987 Feb 12;316(7):379–385. doi: 10.1056/NEJM198702123160705. [DOI] [PubMed] [Google Scholar]
  4. Chapman J. R., Charles P. J., Venables P. J., Thompson P. J., Haslam P. L., Maini R. N., Turner Warwick M. E. Definition and clinical relevance of antibodies to nuclear ribonucleoprotein and other nuclear antigens in patients with cryptogenic fibrosing alveolitis. Am Rev Respir Dis. 1984 Sep;130(3):439–443. doi: 10.1164/arrd.1984.130.3.439. [DOI] [PubMed] [Google Scholar]
  5. Cuturi M. C., Murphy M., Costa-Giomi M. P., Weinmann R., Perussia B., Trinchieri G. Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. J Exp Med. 1987 Jun 1;165(6):1581–1594. doi: 10.1084/jem.165.6.1581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dreisin R. B., Schwarz M. I., Theofilopoulos A. N., Stanford R. E. Circulating immune complexes in the idiopathic interstitial pneumonias. N Engl J Med. 1978 Feb 16;298(7):353–357. doi: 10.1056/NEJM197802162980701. [DOI] [PubMed] [Google Scholar]
  7. Flick D. A., Gifford G. E. Comparison of in vitro cell cytotoxic assays for tumor necrosis factor. J Immunol Methods. 1984 Mar 30;68(1-2):167–175. doi: 10.1016/0022-1759(84)90147-9. [DOI] [PubMed] [Google Scholar]
  8. Fuchs D., Hausen A., Reibnegger G., Werner E. R., Dierich M. P., Wachter H. Neopterin as a marker for activated cell-mediated immunity: application in HIV infection. Immunol Today. 1988 May;9(5):150–155. doi: 10.1016/0167-5699(88)91203-0. [DOI] [PubMed] [Google Scholar]
  9. Fujimoto J., Levy S., Levy R. Spontaneous release of the Leu-2 (T8) molecule from human T cells. J Exp Med. 1983 Sep 1;158(3):752–766. doi: 10.1084/jem.158.3.752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Haslam P. L., Thompson B., Mohammed I., Townsend P. J., Hodson M. E., Holborow E. J., Turner-Warwick M. Circulating immune complexes in patients with cryptogenic fibrosing alveolitis. Clin Exp Immunol. 1979 Sep;37(3):381–390. [PMC free article] [PubMed] [Google Scholar]
  11. Herrmann F., Cannistra S. A., Levine H., Griffin J. D. Expression of interleukin 2 receptors and binding of interleukin 2 by gamma interferon-induced human leukemic and normal monocytic cells. J Exp Med. 1985 Sep 1;162(3):1111–1116. doi: 10.1084/jem.162.3.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Holgate S. T., Haslam P., Turner-Warwick M. The significance of antinuclear and DNA antibodies in cryptogenic fibrosing alveolitis. Thorax. 1983 Jan;38(1):67–70. doi: 10.1136/thx.38.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Huber C., Batchelor J. R., Fuchs D., Hausen A., Lang A., Niederwieser D., Reibnegger G., Swetly P., Troppmair J., Wachter H. Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma. J Exp Med. 1984 Jul 1;160(1):310–316. doi: 10.1084/jem.160.1.310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hunninghake G. W., Gadek J. E., Kawanami O., Ferrans V. J., Crystal R. G. Inflammatory and immune processes in the human lung in health and disease: evaluation by bronchoalveolar lavage. Am J Pathol. 1979 Oct;97(1):149–206. [PMC free article] [PubMed] [Google Scholar]
  15. Josimovic-Alasevic O., Feldmeier H., Zwingenberger K., Harms G., Hahn H., Shrisuphanunt M., Diamantstein T. Interleukin 2 receptor in patients with localized and systemic parasitic diseases. Clin Exp Immunol. 1988 May;72(2):249–254. [PMC free article] [PubMed] [Google Scholar]
  16. Kallenberg C. G., Schilizzi B. M., Beaumont F., Poppema S., De Leij L., The T. H. Expression of class II MHC antigens on alveolar epithelium in fibrosing alveolitis. Clin Exp Immunol. 1987 Jan;67(1):182–190. [PMC free article] [PubMed] [Google Scholar]
  17. Kownatzki E., Kapp A., Uhrich S. Modulation of human neutrophilic granulocyte functions by recombinant human tumor necrosis factor and recombinant human lymphotoxin. Promotion of adherence, inhibition of chemotactic migration and superoxide anion release from adherent cells. Clin Exp Immunol. 1988 Oct;74(1):143–148. [PMC free article] [PubMed] [Google Scholar]
  18. Kradin R. L., Divertie M. B., Colvin R. B., Ramirez J., Ryu J., Carpenter H. A., Bhan A. K. Usual interstitial pneumonitis is a T-cell alveolitis. Clin Immunol Immunopathol. 1986 Aug;40(2):224–235. doi: 10.1016/0090-1229(86)90025-5. [DOI] [PubMed] [Google Scholar]
  19. Lawrence E. C., Brousseau K. P., Berger M. B., Kurman C. C., Marcon L., Nelson D. L. Elevated concentrations of soluble interleukin-2 receptors in serum samples and bronchoalveolar lavage fluids in active sarcoidosis. Am Rev Respir Dis. 1988 Apr;137(4):759–764. doi: 10.1164/ajrccm/137.4.759. [DOI] [PubMed] [Google Scholar]
  20. Ligthart G. J., Corberand J. X., Fournier C., Galanaud P., Hijmans W., Kennes B., Müller-Hermelink H. K., Steinmann G. G. Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev. 1984 Nov;28(1):47–55. doi: 10.1016/0047-6374(84)90152-0. [DOI] [PubMed] [Google Scholar]
  21. Mitchell D. N., Scadding J. G., Heard B. E., Hinson K. F. Sarcoidosis: histopathological definition and clinical diagnosis. J Clin Pathol. 1977 May;30(5):395–408. doi: 10.1136/jcp.30.5.395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nosal A., Schleissner L. A., Mishkin F. S., Lieberman J. Angiotensin-I-converting enzyme and gallium scan in noninvasive evaluation of sarcoidosis. Ann Intern Med. 1979 Mar;90(3):328–331. doi: 10.7326/0003-4819-90-3-328. [DOI] [PubMed] [Google Scholar]
  23. Rubin L. A., Kurman C. C., Biddison W. E., Goldman N. D., Nelson D. L. A monoclonal antibody 7G7/B6, binds to an epitope on the human interleukin-2 (IL-2) receptor that is distinct from that recognized by IL-2 or anti-Tac. Hybridoma. 1985 Summer;4(2):91–102. doi: 10.1089/hyb.1985.4.91. [DOI] [PubMed] [Google Scholar]
  24. Rubin L. A., Kurman C. C., Fritz M. E., Biddison W. E., Boutin B., Yarchoan R., Nelson D. L. Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol. 1985 Nov;135(5):3172–3177. [PubMed] [Google Scholar]
  25. Tomkinson B. E., Brown M. C., Ip S. H., Carrabis S., Sullivan J. L. Soluble CD8 during T cell activation. J Immunol. 1989 Apr 1;142(7):2230–2236. [PubMed] [Google Scholar]
  26. Watters L. C., King T. E., Schwarz M. I., Waldron J. A., Stanford R. E., Cherniack R. M. A clinical, radiographic, and physiologic scoring system for the longitudinal assessment of patients with idiopathic pulmonary fibrosis. Am Rev Respir Dis. 1986 Jan;133(1):97–103. doi: 10.1164/arrd.1986.133.1.97. [DOI] [PubMed] [Google Scholar]
  27. Wolf R. E., Brelsford W. G. Soluble interleukin-2 receptors in systemic lupus erythematosus. Arthritis Rheum. 1988 Jun;31(6):729–735. doi: 10.1002/art.1780310605. [DOI] [PubMed] [Google Scholar]

Articles from Thorax are provided here courtesy of BMJ Publishing Group

RESOURCES