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Increased interleukin 6 production by bronchoalveolar lavage cells in patients with active sarcoidosis

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Abstract

Alveolitis of sarcoidosis is characterized by activated alveolar macrophages (AMs) and T cells. The mediators interleukin-1 (IL-1) and interleukin 6 (IL-6) released by AMs represent essential factors for the progression of the T cells in the cell cycle. The role of IL-1 in pulmonary sarcoidosis has previously been studied; however, the relevance of other mediators (i.e. IL-6) has not yet been evaluated. We measured the spontaneous and lipopolysaccharide (LPS)-induced release of IL-6 and tumor necrosis factor a (TNFα) by bronchoalveolar lavage cells (BAL) and peripheral blood mononuclear cells (PBMNC) in 6 control subjects (group A) and in 15 patients with sarcoidosis, 10 with active (group B), 5 with inactive disease (group C). IL-6 as well as TNFα were spontaneously released by BAL cells of the active group in significantly greater amounts compared to both other groups; IL-6: A, 165.5 pg/ml/24 hr/106 cells (range, 0–604), B, 946 (0–2467), C, 16.6 (0–83); TNFα: A, 162 pg/ml/24 hr/106 cells (0–523), B, 803 (100–17352), C, 100 (0–379). In all groups autologous PBMNC proved to be quiescent, releasing only baseline levels of the cytokines tested. After stimulation with LPS all these cells released great quantities of IL-6 and TNFα. In active disease a positive correlation between IL-6 and TNFα release was observed (r = 0.77, p < 0.02). The present study documents that in active sarcoidosis the spontaneous release of IL-6 by BAL cells parallels the spontaneous release of TNFα. IL-6 is capable of initiating the proliferation and activation of T cells in the lung.

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References

  1. Akira S, Hirano T, Taga T, Kishimoto T (1990) Biology of multifunctional cytokines: IL-6 and related molecules (IL-1 and TNF). FASEB 4:2860–2868

    Google Scholar 

  2. Böyum A (1968) Isolation of mononuclear cells and granulocytes from human blood. Scand J Clin Invest 21 (Suppl):77–89

    Google Scholar 

  3. Bross KJ, Pangalis GA, Staatz CG, Blume KG (1978) Demonstration of cell surface antigens and their antibodies by the peroxidase-antiperoxidase method. Transplantation 25:331–334

    Google Scholar 

  4. Bühlmann AA, Scherer M (1973) Neue Normalwerte für die Vitalkapazität und Totalkapazität der Lunge. Schweiz Med Wochenschr 103:660–671

    Google Scholar 

  5. Costabel U, Bross KJ, Matthys H (1985) The immunoperoxidase slide assay: a new method for the demonstration of the surface antigens on bronchoalveolar cells. Bull Fur Physiopathol Respir 21:381–387

    Google Scholar 

  6. DeRemee R (1983) The roentgenographic staging of sarcoidosis; historic and contemporary perspectives. Chest 83:128–133

    Google Scholar 

  7. Engelmann H, Novick D, Wallach D (1990) Two TNF binding proteins purified from human urine. J Biol Chem 265:1531–1536

    Google Scholar 

  8. Helle M, Brackenhoff JPJ, De Groot ER, Aarden LA (1988) Interleukin-6 is involved in interleukin 1-induced activities. Eur J Immunol 18:957–959

    Google Scholar 

  9. Hirano T, Akira S, Taga T, Kishimoto T (1990) Biological and clinical aspects of interleukin-6. Immunol Today 11:443–449

    Google Scholar 

  10. Hönlinger M, Fuchs D, Hansen A, Reibnegger G, Schönitzer D, Werner ER, Reissigl H, Dierich MP, HW (1989) Serum-Neopterinbestimmung zur zusätzlichen Sicherung der Bluttransfusion. Erfahrungen an 76587 Blutspendern. Dtsch Med Wochenschr 114:172–176

    Google Scholar 

  11. Houssiau FA, Coulie PG, Olive D, Van Snick J (1988) Synergic activation of human cells by interleukin-1 and interleukin-6. Eur J Immunol 18:653–656

    Google Scholar 

  12. Houssiau FA, Coulie PG, Van Snick J (1989) Distinct roles of IL-1 and IL-6 in human T cell activation. J Immunol 143:2520–2524

    Google Scholar 

  13. Hudspith BN, Flint KC, Geraint-James D, Brostoff J, McI Johnson N (1987) Lack of immune deficiency in sarcoidosis: compartmentalisation of the immune response. Thorax 42:250–255

    Google Scholar 

  14. Hunninghake GW (1984) Release of interleukin-1 by alveolar macrophages of patients with active pulmonary sarcoidosis. Am Rev Respir Dis 129:569–572

    Google Scholar 

  15. Hunninghake GW, RG C (1981) Pulmonary sarcoidosis. A disorder mediated by excess helper T-lymphocyte activity at sites of disease activity. N Engl J Med 305:429–434

    CAS  PubMed  Google Scholar 

  16. Jones KP, Reynolds SP, Capper SJ, Kalinka S, Edwards JH, Davies BH (1991) Measurement of interleukin-6 in bronchoalveolar lavage fluid by radioimmunoassay: differences between patients with interstitial lung disease and control subjects. Clin Exp Immunol 83:30–34

    Google Scholar 

  17. Kasahara Y, Miyawaki T, Kimitaka K, Kanegane H, Yachie A, Yokoi T, Taniguchi N (1990) Role of interleukin-6 for differential responsiveness of naive and memory CD4+T cells in CD2-mediated activation. J Exp Med 172:1419–1424

    Google Scholar 

  18. Kishimoto T (1989) The biology of interleukin-6. Blood 74:1–15

    Google Scholar 

  19. Kist A, Ho AD, Räth U, Wiedenmann B, Bauer A, Schlick E, Kirchner H, Männel DN (1988) Decrease of natural killer cell activity and monokine production in peripheral blood of patients treated with recombinant tumor necrosis factor. Blood 72:344–348

    Google Scholar 

  20. Kleinhenz ME, Fujiwara H, Rich EA (1986) Interleukin-1 production by blood monocytes and bronchoalveolar cells in sarcoidosis. Ann NY Acad Sci 465:91–97

    Google Scholar 

  21. Kotloff RM, Little J, A EJ (1990) Human alveolar macrophage and blood monocyte interleukin-6 production. Am J Respir Cell Mol Biol 3:497–505

    Google Scholar 

  22. Kunkel SL, Spengler M, May MA, Spengler R, Larrick J, Remick D (1988) Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem 263:5380–5384

    Google Scholar 

  23. Larsson EL, Iscove NN, Coutinho A (1980) Two distinct factors are required for induction of T-cell growth. Nature 283:664–666

    Google Scholar 

  24. Lem VM, Lipscomb MF, Weissler JC, Nunez G, Ball EJ, Stastny P, Toews GB (1985) Bronchoalveolar cells from sarcoid patients demonstrate enhanced antigen presentation. J Immunol 135:1766–1771

    Google Scholar 

  25. Lorre K, Van Damme J, Verwilghen J, Baroja ML, Ceuppens JL (1990) IL-6 is an accessory signal in the alternative CD2-mediated pathway of T-cell activation. J Immunol 144:4681–4687

    Google Scholar 

  26. Marcy TW, Merril WW, Rankin JA, Reynolds HY (1987) Limitations of using urea to quantify epithelial lining fluid recovered by bronchoalveolar lavage. Ann Rev Respir Dis 135:1276–1280

    Google Scholar 

  27. Martinet N, Charles T, Vaillant P, Vignaud J-M, Lambert J, Martinet Y (1992) Characterization of a tumor necrosis factor-α inhibitor activity in cancer patients. Am J Respir Cell Mol Biol 6:510–515

    Google Scholar 

  28. Milton DK, Gere RJ, Feldman HA, Geaves IA (1990) Endotoxin measurement: Aerosol sampling and application of a new Limulus method. Am Ind Hyg Assoc 51:331–337

    Google Scholar 

  29. Müller-Quernheim J, Pfeifer S, Männel D, Strausz J, Ferlinz R (1992) Lung-restricted activation of the alveolar macrophage/monocyte system in pulmonary sarcoidosis. Am Rev Respir Dis 145:187–192

    Google Scholar 

  30. Müller-Quernheim J, Saltini C, Sondermeyer P, Crystal RG (1986) Compartmentalized activation of the interleukin-2 gene by lung T-lymphocytes in active pulmonary sarcoidosis. J Immunol 137:3475–3483

    Google Scholar 

  31. Novick D, Schulman LM, Chen L, Revel M (1992) Enhancement of interleukin-6 cytostatic effect on human breast carcinoma cells by soluble IL-6 receptor from urine and reversion by monoclonal antibody. Cytokine 4:6–11

    Google Scholar 

  32. Poulter LW (1988) Immune aspects of sarcoidosis. Postgrad Med 64:536–543

    Google Scholar 

  33. Robinson BWS, McLemore T, Crystal RG (1985) Gamma interferon is spontaneously released by alveolar macrophages and lung T-lymphocytes in patients with pulmonary sarcoidosis. J Clin Invest 75:1488–1495

    Google Scholar 

  34. Smith KA, Lachman LB, Oppenheim JJ, Favata M (1980) The functional relationship of the interleukins. J Exp Med 151:1551–1556

    Google Scholar 

  35. Spatafora M, Merendino A, Chiaparra G, Gjomarkaj M, Melis M, Bellia V, Bonsignore G (1989) Lung compartmentalization of increased TNF releasing ability by mononuclear phagocytes in pulmonary sarcoidosis. Chest 96:542–549

    Google Scholar 

  36. Staerz UD, Bevan MJ (1986) Activation of resting T-lymphocytes by a monoclonal antibody directed against an allotypic determinant on the T-cell receptor. Eur J Immunol 16:263–270

    Google Scholar 

  37. Strausz J, Männel DN, Peifer S, Borkowski A, Ferlinz R, Müller-Quernheim J (1991) Spontaneous monokine release by alveolar macrophages in chronic sarcoidosis. Int Arch Allergy Appl Immunol 96:68–75

    Google Scholar 

  38. Suter PM, Suter S, Girardin E, Roux-Lombard P, Grau GE, Dayer J-M (1992) High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis. Am Rev Repir Dis 145:1016–1022

    Google Scholar 

  39. Thomas PD, Hunninghake GW (1987) Current concepts of pathogenesis of sarcoidosis. Am Rev Respir Dis 135:747–760

    Google Scholar 

  40. van Snick JV (1990) Interleukin-6: An overview. Annu Rev Immunol 8:253–278

    Google Scholar 

  41. Venet A, Hance AJ, Saltini C, Robinson BWS, Crystal RG (1985) Enhanced alveolar macrophage-mediated antigen induced T-lymphocyte proliferation in sarcoidosis. J Clin Invest 75:293–301

    Google Scholar 

  42. Ward K, O'Connor C, Odlum C, Fitzgerald MX (1989) Prognostic value of bronchoalveolar lavage in sarcoidosis: the critical influence of disease presentation. Thorax 44:6–12

    Google Scholar 

  43. Wong GG, Clark SC (1988) Multiple actions of interleukin-6 within a cytokine network. Immunol Today 9:137–139

    Google Scholar 

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  1. J. Homolka

    Present address: Ist Lung Department, Charles University, Katerinska 19, 128 00, Prague 2, Czech Republic

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  1. IIIrd Department of Medicine, Pulmonary Division, Johannes Gutenberg University, Langenbeckstrasse 1, 6500, Mainz, Germany

    J. Homolka & J. Müller-Quernheim

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Homolka, J., Müller-Quernheim, J. Increased interleukin 6 production by bronchoalveolar lavage cells in patients with active sarcoidosis. Lung 171, 173–183 (1993). https://doi.org/10.1007/BF00183946

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