Skip to main content
Log in

Inhibitory effects of inhaled flunisolide on inflammatory functions of alveolar macrophages

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

We have studied 15 patients with slight or moderate bronchial obstruction, all of whom were being treated by inhalation of the β-mimetic fenoterol 4×400 μg/day, and 7 of whom were also receiving inhaled flunisolide 2×500 μg/day. The therapy had been given for longer than 1 month in each case. Bronchoscopy and bronchoalveolar lavage (BAL) was done for diagnosis or follow up of bronchial diseases. None of the patients showed signs of any interstitial lung disease.

Conditioned culture supernatants were produced by cultivating alveolar macrophages (AM) for 24 h using standard conditions. To detect all the biological effects both of IL-1α and IL-1 β in the culture supernatants a modification of the standard mouse IL-1 thymocyte bioassay was used. The TNF concentration in culture supernatants was measured by ELISA. Free oxygen radical release by alveolar macrophages was determined by the detection of chemiluminescence.

Both IL-1 and TNF production were significantly lower in patients receiving fenoterol plus flunisolide than in patients on fenoterol alone. In contrast, no difference could be observed in the release of free oxygen radicals from alveolar macrophages.

Thus, for the first time an ex vivo study has revealed an interrelation between inhaled glucocorticoid therapy and inhibition of important mediators of inflammatory processes in the lower respiratory tract.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Abe S, Yamamoto T, Iihara S, Yamazaki M, Mizuno D (1988) A possible role of glucocorticoids: an intrinsic inhibitor of the cytotoxic activity of tumour necrosis factor. Jpn J Cancer Res 79:305–308

    PubMed  CAS  Google Scholar 

  2. Bachwich PR, Lynch JP III, Larrick J, Spengler M, Kunkel SL (1986) Tumour necrosis factor production by human sarcoid alveolar macrophages. Am J Pathol 125:421–425

    PubMed  CAS  Google Scholar 

  3. Barth J, Entzian P, Petermann W (1988) Increased release of free oxygen radicals by phagocytosing and non phagocytosing cells from patients with active pulmonary sarcoidosis as revealed by luminol-dependent chemiluminescence. Klin Wochenschr 66: 292–297

    Article  PubMed  CAS  Google Scholar 

  4. Barth J, Kreipe H, Kiemle-Kallee J, Radzun HJ, Parwaresch MR, Petermann W (1988) Diminished activity of tartrate resistant acid phosphatase in alveolar macrophages with active sarcoidosis. Thorax 43:901–904

    PubMed  CAS  Google Scholar 

  5. Bergstrand H, Bjornson A, Blaschke E, Brattsand R, Eklund A, Larsson K, Linden M (1990) Effects of an inhaled corticosteroid, budesonide, on alveolar macrophage function in smokers. Thorax 45:362–368

    Article  PubMed  CAS  Google Scholar 

  6. Beutler B, Krochin N, Milsark IW, Luedke C, Cerami A (1986) Control of cachectin (tumour necrosis factor) synthesis: mechanisms of endotoxin resistance. Science 232:977–980

    PubMed  CAS  Google Scholar 

  7. Bochner BS, Rutledge BK, Schleimer RP (1987) Interleukin 1 production by human lung tissue. II. Inhibition by anti-inflammatory steroids. J Immunol 139:2303–2307

    PubMed  CAS  Google Scholar 

  8. Carey F, Forder R, Edge MD, Greene AR, Horan MA, Strijbos PJ, Rothwell NJ (1990) Lipocortin 1 fragment modifies pyrogenic actions of cytokines in rats. Am J Physiol 259:R266–269

    PubMed  CAS  Google Scholar 

  9. Chensue SW, Terebuh PD, Remick DG, Scales WE, Kunkel SL (1991) In vivo biologic and immunohistochemical analysis of interleukin-1 alpha, beta and tumour necrosis factor during experimental endotoxemia. Kinetics, Kupffer cell expression, and glucocorticoid effects. Am J Pathol 138:395–402

    PubMed  CAS  Google Scholar 

  10. Cunha FQ, Ferreira SH (1986) The release of a neutrophil chemotactic factor from peritoneal macrophages by endotoxin: inhibition by glucocorticoids. Eur J Pharmacol 129:65–76

    Article  PubMed  CAS  Google Scholar 

  11. Cuturi MC, Murphy M, Costa-Giomi MP, Weimann R, Perussia B, Trinchieri G (1987) Independent regulation of tumour necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. J Exp Med 165:1581–1594

    Article  PubMed  CAS  Google Scholar 

  12. Dinarello CA, Mier JW (1987) Lymphokines-current concepts. N Engl J Med 317:940–945

    Article  PubMed  CAS  Google Scholar 

  13. Erkkila S, Froseth B, Hellstrom PE, Kaltiokallio K, Taskinen E, Viljanen A, Viljanen B, Selroos O (1988) Inhaled budesonide influences cellular and biochemical abnormalities in pulmonary sarcoidosis. Sarcoidosis 5:106–110

    PubMed  CAS  Google Scholar 

  14. Hunninghake GW (1984) Release of interleukin 1 by alveolar macrophages of patients with active pulmonary sarcoidosis. Am Rev Respir Dis 124:569–572

    Google Scholar 

  15. Iwamoto S, Takeda K (1990) Possible cytotoxic mechanisms of TNF in vitro. Hum Cell 3:107–112

    PubMed  CAS  Google Scholar 

  16. Kelley J. Cytokines of the lung (1990) Am Rev Respir Dis 141: 765–788

    PubMed  CAS  Google Scholar 

  17. Kreipe H, Radzun HJ, Rudolph P, Barth J, Hansmann ML, Heidorn K, Parawaresch MR (1988) Multinucleated giant cells generated in vitro: Terminally differentiated macrophages with down regulated c-fms expression. Am J Pathol 130:232–243

    PubMed  CAS  Google Scholar 

  18. Lee SW, Tsou AP, Chan H, Thomas J, Petrie K, Eugui EM, Allison AC (1988) Glucocorticoids selectively inhibit the transcription of the interleukin 1 beta gene and decrease the stability of interleukin 1 beta mRNA. Proc Natl Acad Sci USA 85:1204–1208

    Article  PubMed  CAS  Google Scholar 

  19. Maridonneau-Parini I, Errasfa M, Russo-Marie F (1989) Inhibition of O2-generation by dexamethasone is mimicked by lipocortin I in alveolar macrophages. J Clin Invest 83:1936–1940

    Article  PubMed  CAS  Google Scholar 

  20. Mizel SB, Dayer JM, Krane SM, Mergenhagen SE (1981) Stimulation of rheumatoid synovial cell collagenase and prostaglandin production by partially purified lymphocyte-activating factor (interleukin 1) Proc Natl Acad Sci USA 78:2474–2477

    Article  PubMed  CAS  Google Scholar 

  21. Old LJ (1985) Tumour necrosis factor (TNF). Science 230:630–632

    PubMed  CAS  Google Scholar 

  22. Piccolella E, Vismara D, Lombardi G, Guerrtore D, Piantelli M, Ranelletti FO (1985) Effect of glucocorticoids on the development of suppressive activity in human lymphocyte response to a polysaccharide purified from Candida albicans. J Immunol 134: 1160–1171

    Google Scholar 

  23. Reynolds HY (1987) Bronchoalveolar lavage. Am Rev Respir Dis 135:250–263

    PubMed  CAS  Google Scholar 

  24. Schleimer RP (1990) Effects of glucocorticoids on inflammatory cells relevant to their therapeutic applications in asthma. Am Rev Respir Dis 141:S59-S69

    PubMed  CAS  Google Scholar 

  25. Selroos O (1986) Use of budesonide in the treatment of pulmonary sarcoidosis. Ann NY Acad Sci 465: 713–721

    PubMed  CAS  Google Scholar 

  26. Szefler SJ, Norton CE, Ball B, Gross JM, Aida Y, Pabst MJ (1989) IFN-gamma and LPS overcome glucocorticoid inhibition of priming for superoxide release in human monocytes. Evidence that secretion of IL-1 and tumour necrosis factor-alpha is not essential for monocyte priming. J Immunol 142:3985–3992

    PubMed  CAS  Google Scholar 

  27. Tsujimoto M, Okamura N, Adachi H (1988) Dexamethasone inhibits the cytotoxic activity of tumour necrosis factor. Biochem Biophys Res Commun 153:109–115

    Article  PubMed  CAS  Google Scholar 

  28. Vadas P, Pruzanski W (1990) Phospholipase A2 activation is the pivotal step in the effector pathway of inflammation. Adv Exp Med Biol 275:83–101

    PubMed  CAS  Google Scholar 

  29. Waage A; Bakke O (1988) Glucocorticoids suppress the production of tumour necrosis factor by lipopolysaccharide-stimulated human monocytes. Immunology 63:299–302

    PubMed  CAS  Google Scholar 

  30. Wewers MD, Saltini C, Sellers S, Tocci MJ, Bayne EK, Schmidt JA, Crystal RG (1987) Evaluation of alveolar macrophages in normal and in individuals with active pulmonary sarcoidosis for the spontaneous expression of the interleukin 1 beta gene. Cell Immunol 107:479–485

    Article  PubMed  CAS  Google Scholar 

  31. Zuckerman SH, Shellhaas J, Butler LD (1989) Differential regulation of lipopolysaccharide-induced interleukin 1 and tumour necrosis factor synthesis: effects of endogenous and exogenous glucocorticoids and the role of the pituitary-adrenal axis. Eur J Immunol 19:301–305

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bewig, B., Barth, J. Inhibitory effects of inhaled flunisolide on inflammatory functions of alveolar macrophages. Eur J Clin Pharmacol 44, 541–544 (1993). https://doi.org/10.1007/BF02440855

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02440855

Key words

Navigation