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Cytokines

TNFα, interleukin-10 and interleukin-18 expression in cells of the bronchoalveolar lavage in patients with pulmonary complications following bone marrow or peripheral stem cell transplantation: a preliminary study

Abstract

Pulmonary complications pose a major clinical problem after bone marrow transplantation (BMT) or peripheral blood stem cell transplantation (PBSCT). The underlying pathophysiological mechanisms are under investigation. Twenty patients with infectious or non-infectious pulmonary complications after BMT or PBSCT underwent bronchoalveolar lavage (BAL) and tumor necrosis factor-α (TNFα), interleukin-10 (IL-10) and interleukin-18 (IL-18) mRNA expression was determined in BAL cells in comparison to 11 healthy volunteers. Patients were divided into two groups (infectious pneumonia, n = 14 or idiopathic pneumonia syndrome (IPS)/bronchiolitis obliterans (BO), n = 6). TNFα expression was significantly increased in both patient groups compared to the control (0.40 ± 0.07 and 0.39 ± 0.09 vs 0.15 ± 0.05; P < 0.05; semiquantitative PCR analysis; mean ± s.e.m.). IL-10 expression was significantly elevated the group of patients with infectious pneumonia in comparison to normal controls (0.15 ± 0.06 vs 0.01 ± 0.01; P < 0.05) but not in patients with IPS/BO (0.05 ± 0.04; P > 0.05). However, IL-10 was not expressed in BAL cells of all patients and control individuals. IL-18 expression was significantly decreased in the both patient groups (1.47 ± 0.24 and 1.79 ± 0.63) in comparison to the control group (4.29 ± 0.77; P < 0.05). Survival analysis showed a significant association between elevation of TNFα and poor prognosis (P < 0.05). These results highlight the immunoregulatory disturbances in the lungs after BMT/PBSCT.

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References

  1. Quabeck K . The lung as a critical organ in marrow transplantation Bone Marrow Transplant 1994 14: (Suppl. 4) S19 S28

    PubMed  Google Scholar 

  2. Stover DE, Zaman MB, Hajdn SI et al. Bronchoalveolar lavage in the diagnosis of diffuse pulmonary infiltrates in the immunosuppressed host Ann Intern Med 1984 101: 1 7

    Article  CAS  PubMed  Google Scholar 

  3. Kahn FW, Jones JM . Diagnosing bacterial respiratory infection by bronchoalveolar lavage J Infect Dis 1987 155: 862 869

    Article  CAS  PubMed  Google Scholar 

  4. Quabeck K, Teschler H, Beelen DW et al. Diagnostic value of bronchoalveolar lavage in bone marrow transplant patients with pulmonary complications Am Rev Respir Dis 1991 143: A113 (Abstr.)

    Google Scholar 

  5. Crawford SW, Bowden RA, Hackman RC et al. Rapid detection of cytomegalovirus pulmonary infection by bronchoalveolar lavage and centrifugation culture Ann Intern Med 1988 108: 180 185

    Article  CAS  PubMed  Google Scholar 

  6. Leskinen R, Taskinen E, Volin L et al. Use of bronchoalveolar lavage cytology and determination of protein contents in pulmonary complications of bone marrow transplant recipients Bone Marrow Transplant 1990 5: 241 245

    CAS  PubMed  Google Scholar 

  7. de la Camara R, Gion R, Marron C et al. Bronchoalveolar lavage cell composition in allogeneis bone marrow transplantation patients without symptomatic lung complications Bone Marrow Transplant 1997 20: 1087 1093

    Article  CAS  PubMed  Google Scholar 

  8. Slavin M, Dobbs S, Crawford S, Bowden R . Interleukin-2, interferon-( and natural killer cell activity in bronchoalveolar lavage fluid from marrow transplant recipients with cytomegalovirus pneumonia Bone Marrow Transplant 1993 11: 113 118

    CAS  PubMed  Google Scholar 

  9. Clark JG, Madtes DK, Martin TR et al. Idiopathic pneumonia after bone marrow transplantation: cytokine activation and lipopolysaccharide amplification in the bronchoalveolar compartment Crit Care Med 1999 27: 1800 1806

    Article  CAS  PubMed  Google Scholar 

  10. Liem LM, van Houwelingen HC, Goulmy E . Serum cytokine levels after HLA-identical bone marrow transplantation Transplantation 1998 66: 863 871

    Article  CAS  PubMed  Google Scholar 

  11. Holler E, Kolb HJ, Möller A et al. Increased serum levels of tumor necrosis factor α precede major complications of bone marrow transplantation Blood 1990 75: 1011 1016

    CAS  PubMed  Google Scholar 

  12. Rowbottom AW, Riches PG, Downie C, Hobbs JR . Monitoring cytokine production in peripheral blood during acute graft-versus-host disease following allogeneic bone marrow transplantation Bone Marrow Transplant 1993 12: 635 641

    CAS  PubMed  Google Scholar 

  13. Vogelsang GB, Hess AD . Graft-versus-host disease: new directions for a persistent problem Blood 1994 84: 2061 2067

    CAS  PubMed  Google Scholar 

  14. Ferrara JLM, Cooke KR, Pan L, Krenger W . The immunopathophysiology of acute graft-versus-host disease Stem Cells 1996 14: 473 489

    Article  CAS  PubMed  Google Scholar 

  15. Nakamura H, Komatsu K, Ayaki M et al. Serum levels of soluble IL-12, IL-18, and IFN-γ in patients with acute graft-versus-host disease after allogeneic bone marrow transplantation J Allergy Clin Immunol 2000 106: S45 50

    Article  CAS  PubMed  Google Scholar 

  16. Fujimori Y, Takatsuka H, Takemoto Y et al. Elevated interleukin (IL)-18 levels during acute graft-versus-host disease after allogeneic bone marrow transplantation Br J Haematol 2000 109: 652 657

    Article  CAS  PubMed  Google Scholar 

  17. Fiorentino DF, Zlotnik A, Mosmann TR et al. IL-10 inhibits cytokine production by activated macrophages J Immunol 1991 147: 3815 3822

    CAS  PubMed  Google Scholar 

  18. Frankenberger M, Sternsdorf T, Pechumer H et al. Differential cytokine expression in human blood moncyte subpopulations: a polymerase chain reaction analysis Blood 1996 87: 373 377

    CAS  PubMed  Google Scholar 

  19. Puren AJ, Fantuzzi G, Dinarello CA . Gene expression, synthesis and secretion of interleukin 18 and interleukin 1 beta are differentially regulated in human blood mononuclear and mouse spleen cells Proc Natl Acad Sci USA 1999 96: 2256 2261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hanncock A, Armstrong L, Gama R, Millar A . Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung Am J Respir Cell Mol Biol 1998 18: 60 65

    Article  Google Scholar 

  21. Sparrelid E, Emanuel D, Fehniger T et al. Interstitial pneumonitis in bone marrow transplant recipients is associated with local production of TH2-type cytokines and lack of T cell-mediated cytotoxicity Transplantation 1997 63: 1782 1789

    Article  CAS  PubMed  Google Scholar 

  22. Shankar G, Bryson JS, Jennings CD et al. Idiopathic pneumonia syndrome in mice after allogeneic bone marrow transplantation Am J Respir Cell Mol Biol 1998 18: 235 242

    Article  CAS  PubMed  Google Scholar 

  23. Boehler A, Bai XH, Liu M et al. Upregulation of T-helper 1 cytokines and chemokine expression in post-transplant airway obliteration Am J Respir Crit Care Med 1999 159: 1910 1917

    Article  CAS  PubMed  Google Scholar 

  24. Thomas DE, Ramberg E, Sale GE et al. Direct evidence for a bone marrow origin ot the alveolar macrophage in man Science 1976 192: 1016 1018

    Article  CAS  PubMed  Google Scholar 

  25. Milburn HJ, Prentice HG, Poulter LW . Abnormal alveolar macrophage populations in bone marrow transplant recipients with pneumonitis Eur Respir J 1993 6: 1295 1300

    CAS  PubMed  Google Scholar 

  26. Zecchina G, Novick D, Rubinstein M et al. Interleukin-19 binding protein in acute graft versus host disease and engraftment following allogeneic peripheral blood stem cell transplants J Hematother Stem Cell Res 2001 10: 769 776

    Article  CAS  PubMed  Google Scholar 

  27. Reddy P, Teshima T, Kukuruga M et al. Interleukin-18 regulates acute graft-versus-host disease by enhancing Fas-mediated donor T cell apoptosis J Exp Med 2001 194: 1433 1440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Miettinen M, Matikainen S, Voupio-Varkila J et al. Lactobacilli and streptococci induce interleukin-12 (IL-12), IL-18, and gamma interferon production in human peripheral blood mononuclear cells Infect Immun 1998 66: 6058 6062

    CAS  PubMed  PubMed Central  Google Scholar 

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Hauber, HP., Mikkilä, A., Erich, J. et al. TNFα, interleukin-10 and interleukin-18 expression in cells of the bronchoalveolar lavage in patients with pulmonary complications following bone marrow or peripheral stem cell transplantation: a preliminary study. Bone Marrow Transplant 30, 485–490 (2002). https://doi.org/10.1038/sj.bmt.1703722

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