Skip to main content
NCBI home page
Mediators of Inflammation logoLink to Mediators of Inflammation
. 1992;1(5):319–322. doi: 10.1155/S0962935192000474

Suppressive effect of TNF-α and IL-1 on alveolar fibroblast proliferation in sarcoidosis

E Fireman 1,✉, D Aderka 2, S Ben Efraim 3, J Greif 1, D Wallach 4, M Topilsky 1
PMCID: PMC2365356  PMID: 18475478

Abstract

The nature of soluble factors that regulate fibroblast proliferation have not been finally characterized. Our aim was to study the role of tumour necrosis factor α (TNF-α) and interleukin-1 (IL-1) in the suppressive activity of alveolar macrophages on autologous lung fibroblasts proliferation in sarcoidosis. We found that supernatants recovered from alveolar macrophages suppressed the proliferation of alveolar fibroblast in sarcoidosis by 35.5 ± 1.13% compared to 3 ± 16% in controls (p < 0.001 between the two groups). This suppression correlated with high content of TNF-α and IL-1 in sarcoidosis patients stage II-III (7.7 ± 2.9 ng/ml TNF-α and 157 ± 53 U/ml IL-1 compared to 3.4 ± 2.4 ng/ml TNF-α and 43 U/ml IL-1 in controls; p < 0.01 and p < 0.001, respectively). Both cytokines in sarcoidosis stage I were within the normal ranges. Exogenous TNF-α (1000-0.5 ng/ml) and IL-1 (500-0.24 ng/ml) had an additive suppressive activity on fibroblast proliferation which was partially reversed by indomethacin.

Full Text

The Full Text of this article is available as a PDF (415.4 KB).

Selected References

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

  1. Bachwich P. R., Lynch J. P., 3rd, Kunkel S. L. Arachidonic acid metabolism is altered in sarcoid alveolar macrophages. Clin Immunol Immunopathol. 1987 Jan;42(1):27–37. doi: 10.1016/0090-1229(87)90170-x. [DOI] [PubMed] [Google Scholar]
  2. Bitterman P. B., Rennard S. I., Hunninghake G. W., Crystal R. G. Human alveolar macrophage growth factor for fibroblasts. Regulation and partial characterization. J Clin Invest. 1982 Oct;70(4):806–822. doi: 10.1172/JCI110677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bitterman P. B., Wewers M. D., Rennard S. I., Adelberg S., Crystal R. G. Modulation of alveolar macrophage-driven fibroblast proliferation by alternative macrophage mediators. J Clin Invest. 1986 Mar;77(3):700–708. doi: 10.1172/JCI112364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dayer J. M., Beutler B., Cerami A. Cachectin/tumor necrosis factor stimulates collagenase and prostaglandin E2 production by human synovial cells and dermal fibroblasts. J Exp Med. 1985 Dec 1;162(6):2163–2168. doi: 10.1084/jem.162.6.2163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Elias J. A., Gustilo K., Freundlich B. Human alveolar macrophage and blood monocyte inhibition of fibroblast proliferation. Evidence for synergy between interleukin-1 and tumor necrosis factor. Am Rev Respir Dis. 1988 Dec;138(6):1595–1603. doi: 10.1164/ajrccm/138.6.1595. [DOI] [PubMed] [Google Scholar]
  6. Elias J. A., Jimenez S. A., Freundlich B. Recombinant gamma, alpha, and beta interferon regulation of human lung fibroblast proliferation. Am Rev Respir Dis. 1987 Jan;135(1):62–65. doi: 10.1164/arrd.1987.135.1.62. [DOI] [PubMed] [Google Scholar]
  7. Elias J. A., Rossman M. D., Daniele R. P. Blood and lung mononuclear cell inhibition of fibroblast growth in sarcoidosis. Am Rev Respir Dis. 1984 Dec;130(6):1050–1057. doi: 10.1164/arrd.1984.130.6.1050. [DOI] [PubMed] [Google Scholar]
  8. Elias J. A., Rossman M. D., Zurier R. B., Daniele R. P. Human alveolar macrophage inhibition of lung fibroblast growth. A prostaglandin-dependent process. Am Rev Respir Dis. 1985 Jan;131(1):94–99. doi: 10.1164/arrd.1985.131.1.94. [DOI] [PubMed] [Google Scholar]
  9. Elias J. A., Rossman M. D., Zurier R. B., Daniele R. P. Human alveolar macrophage inhibition of lung fibroblast growth. A prostaglandin-dependent process. Am Rev Respir Dis. 1985 Jan;131(1):94–99. doi: 10.1164/arrd.1985.131.1.94. [DOI] [PubMed] [Google Scholar]
  10. Elias J. A. Tumor necrosis factor interacts with interleukin-1 and interferons to inhibit fibroblast proliferation via fibroblast prostaglandin-dependent and -independent mechanisms. Am Rev Respir Dis. 1988 Sep;138(3):652–658. doi: 10.1164/ajrccm/138.3.652. [DOI] [PubMed] [Google Scholar]
  11. Fireman E., Ben Efraim S., Greif J., Alguetti A., Ayalon D., Topilsky M. Suppressive activity of alveolar macrophages and blood monocytes from interstitial lung diseases: role of released soluble factors. Int J Immunopharmacol. 1989;11(7):751–760. doi: 10.1016/0192-0561(89)90129-x. [DOI] [PubMed] [Google Scholar]
  12. Fireman E., Ben Efraim S., Messer G., Dabush S., Greif J., Topilsky M. Cell-free supernatants of sarcoid alveolar macrophages suppress proliferation of sarcoid alveolar fibroblasts. Clin Immunol Immunopathol. 1991 Jun;59(3):368–378. doi: 10.1016/0090-1229(91)90032-6. [DOI] [PubMed] [Google Scholar]
  13. Gowen M., Wood D. D., Russell R. G. Stimulation of the proliferation of human bone cells in vitro by human monocyte products with interleukin-1 activity. J Clin Invest. 1985 Apr;75(4):1223–1229. doi: 10.1172/JCI111819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hunninghake G. W. Release of interleukin-1 by alveolar macrophages of patients with active pulmonary sarcoidosis. Am Rev Respir Dis. 1984 Apr;129(4):569–572. [PubMed] [Google Scholar]
  15. Sugarman B. J., Aggarwal B. B., Hass P. E., Figari I. S., Palladino M. A., Jr, Shepard H. M. Recombinant human tumor necrosis factor-alpha: effects on proliferation of normal and transformed cells in vitro. Science. 1985 Nov 22;230(4728):943–945. doi: 10.1126/science.3933111. [DOI] [PubMed] [Google Scholar]

Articles from Mediators of Inflammation are provided here courtesy of Wiley

RESOURCES