Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1993 Apr;92(1):23–26. doi: 10.1111/j.1365-2249.1993.tb05942.x

High circulating leukaemia inhibitory factor (LIF) in patients with giant cell arteritis: independent regulation of LIF and IL-6 under corticosteroid therapy.

J C Lecron 1, P Roblot 1, S Chevalier 1, F Morel 1, E Alderman 1, J Gombert 1, H Gascan 1
PMCID: PMC1554861  PMID: 8096803

Abstract

Leukaemia inhibitory factor (LIF) is a cytokine which possesses a wide range of biological activities including, like IL-6, the capacity to stimulate acute phase protein (APP) synthesis. We have developed a sensitive and specific ELISA for human LIF, and tested the circulating cytokine levels in various disease states, some of which are associated with inflammation. LIF was detected in 11/20 sera from patients with giant cell arteritis (GCA), a vasculitis syndrome affecting particularly the temporal artery, characterized by panarteritis with inflammatory cell infiltration. LIF levels were considerably elevated in some patients who also displayed elevated levels of IL-6 and C-reactive protein (CRP); however, no correlation was observed between the levels of circulating LIF and levels of IL-6 or CRP. Furthermore, LIF levels were not affected by corticosteroid therapy, whereas IL-6 and CRP decreased rapidly, as clinical symptoms resolved. A putative role for LIF in the persistence of histological lesions is discussed. This is the first report of the presence of circulating LIF in sera. These results are in agreement with the complexity of induced inflammatory cytokines and corticoid regulation of APP synthesis observed in vitro and in vivo.

Full text

PDF
23

Selected References

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

  1. Austin L., Burgess A. W. Stimulation of myoblast proliferation in culture by leukaemia inhibitory factor and other cytokines. J Neurol Sci. 1991 Feb;101(2):193–197. doi: 10.1016/0022-510x(91)90045-9. [DOI] [PubMed] [Google Scholar]
  2. Baumann H., Wong G. G. Hepatocyte-stimulating factor III shares structural and functional identity with leukemia-inhibitory factor. J Immunol. 1989 Aug 15;143(4):1163–1167. [PubMed] [Google Scholar]
  3. Brown T. J., Rowe J. M., Liu J. W., Shoyab M. Regulation of IL-6 expression by oncostatin M. J Immunol. 1991 Oct 1;147(7):2175–2180. [PubMed] [Google Scholar]
  4. Ferrara N., Winer J., Henzel W. J. Pituitary follicular cells secrete an inhibitor of aortic endothelial cell growth: identification as leukemia inhibitory factor. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):698–702. doi: 10.1073/pnas.89.2.698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gascan H., Anegón I., Praloran V., Naulet J., Godard A., Soulillou J. P., Jacques Y. Constitutive production of human interleukin for DA cells/leukemia inhibitory factor by human tumor cell lines derived from various tissues. J Immunol. 1990 Apr 1;144(7):2592–2598. [PubMed] [Google Scholar]
  6. Gascan H., Godard A., Ferenz C., Naulet J., Praloran V., Peyrat M. A., Hewick R., Jacques Y., Moreau J. F., Soulillou J. P. Characterization and NH2-terminal amino acid sequence of natural human interleukin for DA cells: leukemia inhibitory factor. Differentiation inhibitory activity secreted by a T lymphoma cell line. J Biol Chem. 1989 Dec 25;264(36):21509–21515. [PubMed] [Google Scholar]
  7. Gauldie J., Richards C., Harnish D., Lansdorp P., Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251–7255. doi: 10.1073/pnas.84.20.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gearing D. P., Comeau M. R., Friend D. J., Gimpel S. D., Thut C. J., McGourty J., Brasher K. K., King J. A., Gillis S., Mosley B. The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor. Science. 1992 Mar 13;255(5050):1434–1437. doi: 10.1126/science.1542794. [DOI] [PubMed] [Google Scholar]
  9. Gearing D. P., Thut C. J., VandeBos T., Gimpel S. D., Delaney P. B., King J., Price V., Cosman D., Beckmann M. P. Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130. EMBO J. 1991 Oct;10(10):2839–2848. doi: 10.1002/j.1460-2075.1991.tb07833.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gonzalez E. B., Varner W. T., Lisse J. R., Daniels J. C., Hokanson J. A. Giant-cell arteritis in the southern United States. An 11-year retrospective study from the Texas Gulf Coast. Arch Intern Med. 1989 Jul;149(7):1561–1565. [PubMed] [Google Scholar]
  11. Gough N. M., Gearing D. P., King J. A., Willson T. A., Hilton D. J., Nicola N. A., Metcalf D. Molecular cloning and expression of the human homologue of the murine gene encoding myeloid leukemia-inhibitory factor. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2623–2627. doi: 10.1073/pnas.85.8.2623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hall S., Persellin S., Lie J. T., O'Brien P. C., Kurland L. T., Hunder G. G. The therapeutic impact of temporal artery biopsy. Lancet. 1983 Nov 26;2(8361):1217–1220. doi: 10.1016/s0140-6736(83)91269-2. [DOI] [PubMed] [Google Scholar]
  13. Heinrich P. C., Castell J. V., Andus T. Interleukin-6 and the acute phase response. Biochem J. 1990 Feb 1;265(3):621–636. doi: 10.1042/bj2650621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hilton D. J., Nicola N. A., Metcalf D. Distribution and comparison of receptors for leukemia inhibitory factor on murine hemopoietic and hepatic cells. J Cell Physiol. 1991 Feb;146(2):207–215. doi: 10.1002/jcp.1041460204. [DOI] [PubMed] [Google Scholar]
  15. Ip N. Y., Nye S. H., Boulton T. G., Davis S., Taga T., Li Y., Birren S. J., Yasukawa K., Kishimoto T., Anderson D. J. CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130. Cell. 1992 Jun 26;69(7):1121–1132. doi: 10.1016/0092-8674(92)90634-o. [DOI] [PubMed] [Google Scholar]
  16. Mackiewicz A., Speroff T., Ganapathi M. K., Kushner I. Effects of cytokine combinations on acute phase protein production in two human hepatoma cell lines. J Immunol. 1991 May 1;146(9):3032–3037. [PubMed] [Google Scholar]
  17. Metcalf D., Gearing D. P. Fatal syndrome in mice engrafted with cells producing high levels of the leukemia inhibitory factor. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5948–5952. doi: 10.1073/pnas.86.15.5948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Miles S. A., Martínez-Maza O., Rezai A., Magpantay L., Kishimoto T., Nakamura S., Radka S. F., Linsley P. S. Oncostatin M as a potent mitogen for AIDS-Kaposi's sarcoma-derived cells. Science. 1992 Mar 13;255(5050):1432–1434. doi: 10.1126/science.1542793. [DOI] [PubMed] [Google Scholar]
  19. Moreau J. F., Donaldson D. D., Bennett F., Witek-Giannotti J., Clark S. C., Wong G. G. Leukaemia inhibitory factor is identical to the myeloid growth factor human interleukin for DA cells. Nature. 1988 Dec 15;336(6200):690–692. doi: 10.1038/336690a0. [DOI] [PubMed] [Google Scholar]
  20. Nair B. C., DeVico A. L., Nakamura S., Copeland T. D., Chen Y., Patel A., O'Neil T., Oroszlan S., Gallo R. C., Sarngadharan M. G. Identification of a major growth factor for AIDS-Kaposi's sarcoma cells as oncostatin M. Science. 1992 Mar 13;255(5050):1430–1432. doi: 10.1126/science.1542792. [DOI] [PubMed] [Google Scholar]
  21. Ray A., LaForge K. S., Sehgal P. B. On the mechanism for efficient repression of the interleukin-6 promoter by glucocorticoids: enhancer, TATA box, and RNA start site (Inr motif) occlusion. Mol Cell Biol. 1990 Nov;10(11):5736–5746. doi: 10.1128/mcb.10.11.5736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Smith A. G., Heath J. K., Donaldson D. D., Wong G. G., Moreau J., Stahl M., Rogers D. Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides. Nature. 1988 Dec 15;336(6200):688–690. doi: 10.1038/336688a0. [DOI] [PubMed] [Google Scholar]
  23. Waage A., Slupphaug G., Shalaby R. Glucocorticoids inhibit the production of IL6 from monocytes, endothelial cells and fibroblasts. Eur J Immunol. 1990 Nov;20(11):2439–2443. doi: 10.1002/eji.1830201112. [DOI] [PubMed] [Google Scholar]
  24. Yamamori T., Fukada K., Aebersold R., Korsching S., Fann M. J., Patterson P. H. The cholinergic neuronal differentiation factor from heart cells is identical to leukemia inhibitory factor. Science. 1989 Dec 15;246(4936):1412–1416. doi: 10.1126/science.2512641. [DOI] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES