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. 1989 Mar;66(3):376–383.

Control by IFN-gamma and PGE2 of TNF alpha and IL-1 production by human monocytes.

P H Hart 1, G A Whitty 1, D S Piccoli 1, J A Hamilton 1
PMCID: PMC1385223  PMID: 2495247

Abstract

There have been suggestions that the production of pro-inflammatory mediators by human monocytes in response to interferon-gamma (IFN-gamma) may be controlled by changes in prostaglandins. Therefore we investigated tumour necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) activities and prostaglandin E2 (PGE2) levels in the supernatants of highly purified human monocytes cultured for 18 hr with recombinant human IFN-gamma. IFN-gamma (100 U/ml) did not stimulate monocytes isolated by counter-current centrifugal elutriation for detectable TNF alpha or IL-1 activities, or PGE2 production. However, IFN-gamma synergistically enhanced lipopolysaccharide (LPS)-induced TNF alpha and IL-1 activities. In contrast, there was no consistent change in PGE2 levels upon addition of IFN-gamma to LPS-treated monocyte cultures. The TNF alpha and IL-1 activities induced by LPS and by LPS with IFN-gamma were reduced by PGE2, and stimulated by indomethacin. As reported previously for IL-1 activities, the regulation by cyclo-oxygenase products of TNF alpha activities reflected predominantly a control of the production of immunoreactive TNF alpha, rather than the measurement of TNF alpha bio-activity. However, the addition of indomethacin or PGE2 to monocyte cultures did not change the extent of IFN-gamma synergy with LPS for increased TNF alpha and IL-1 activities. The results of this study suggest that, despite control by cyclo-oxygenase products of TNF alpha and IL-1 production in human monocytes, IFN-gamma may enhance TNF alpha and IL-1 activities independently of this regulatory mechanism. These findings are contrary to those suggested for the regulation by prostanoids of IL-1 production by murine macrophages.

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Selected References

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  1. Arenzana-Seisdedos F., Virelizier J. L., Fiers W. Interferons as macrophage-activating factors. III. Preferential effects of interferon-gamma on the interleukin 1 secretory potential of fresh or aged human monocytes. J Immunol. 1985 Apr;134(4):2444–2448. [PubMed] [Google Scholar]
  2. Boraschi D., Censini S., Tagliabue A. Interferon-gamma reduces macrophage-suppressive activity by inhibiting prostaglandin E2 release and inducing interleukin 1 production. J Immunol. 1984 Aug;133(2):764–768. [PubMed] [Google Scholar]
  3. Browning J. L., Ribolini A. Interferon blocks interleukin 1-induced prostaglandin release from human peripheral monocytes. J Immunol. 1987 May 1;138(9):2857–2863. [PubMed] [Google Scholar]
  4. Cavaillon J. M., Haeffner-Cavaillon N. Polymyxin-B inhibition of LPS-induced interleukin-1 secretion by human monocytes is dependent upon the LPS origin. Mol Immunol. 1986 Sep;23(9):965–969. doi: 10.1016/0161-5890(86)90127-6. [DOI] [PubMed] [Google Scholar]
  5. Dinarello C. A., Cannon J. G., Wolff S. M., Bernheim H. A., Beutler B., Cerami A., Figari I. S., Palladino M. A., Jr, O'Connor J. V. Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1. J Exp Med. 1986 Jun 1;163(6):1433–1450. doi: 10.1084/jem.163.6.1433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Flick D. A., Gifford G. E. Comparison of in vitro cell cytotoxic assays for tumor necrosis factor. J Immunol Methods. 1984 Mar 30;68(1-2):167–175. doi: 10.1016/0022-1759(84)90147-9. [DOI] [PubMed] [Google Scholar]
  7. Ghiara P., Boraschi D., Nencioni L., Ghezzi P., Tagliabue A. Enhancement of in vivo immune response by tumor necrosis factor. J Immunol. 1987 Dec 1;139(11):3676–3679. [PubMed] [Google Scholar]
  8. Gifford G. E., Lohmann-Matthes M. L. Gamma interferon priming of mouse and human macrophages for induction of tumor necrosis factor production by bacterial lipopolysaccharide. J Natl Cancer Inst. 1987 Jan;78(1):121–124. doi: 10.1093/jnci/78.1.121. [DOI] [PubMed] [Google Scholar]
  9. Gregory S. A., Kornbluth R. S., Helin H., Remold H. G., Edgington T. S. Monocyte procoagulant inducing factor: a lymphokine involved in the T cell-instructed monocyte procoagulant response to antigen. J Immunol. 1986 Nov 15;137(10):3231–3239. [PubMed] [Google Scholar]
  10. Hamilton T. A., Becton D. L., Somers S. D., Gray P. W., Adams D. O. Interferon-gamma modulates protein kinase C activity in murine peritoneal macrophages. J Biol Chem. 1985 Feb 10;260(3):1378–1381. [PubMed] [Google Scholar]
  11. Hart P. H., Whitty G. A., Piccoli D. S., Hamilton J. A. Synergistic activation of human monocytes by granulocyte-macrophage colony-stimulating factor and IFN-gamma. Increased TNF-alpha but not IL-1 activity. J Immunol. 1988 Sep 1;141(5):1516–1521. [PubMed] [Google Scholar]
  12. Khansari N., Chou Y. K., Fudenberg H. H. Human monocyte heterogeneity: interleukin 1 and prostaglandin E2 production by separate subsets. Eur J Immunol. 1985 Jan;15(1):48–51. doi: 10.1002/eji.1830150110. [DOI] [PubMed] [Google Scholar]
  13. Knudsen P. J., Dinarello C. A., Strom T. B. Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate. J Immunol. 1986 Nov 15;137(10):3189–3194. [PubMed] [Google Scholar]
  14. Koerner T. J., Adams D. O., Hamilton T. A. Regulation of tumor necrosis factor (TNF) expression: interferon-gamma enhances the accumulation of mRNA for TNF induced by lipopolysaccharide in murine peritoneal macrophages. Cell Immunol. 1987 Oct 15;109(2):437–443. doi: 10.1016/0008-8749(87)90326-1. [DOI] [PubMed] [Google Scholar]
  15. Kunkel S. L., Chensue S. W., Phan S. H. Prostaglandins as endogenous mediators of interleukin 1 production. J Immunol. 1986 Jan;136(1):186–192. [PubMed] [Google Scholar]
  16. Kunkel S. L., Spengler M., May M. A., Spengler R., Larrick J., Remick D. Prostaglandin E2 regulates macrophage-derived tumor necrosis factor gene expression. J Biol Chem. 1988 Apr 15;263(11):5380–5384. [PubMed] [Google Scholar]
  17. Kunkel S. L., Wiggins R. C., Chensue S. W., Larrick J. Regulation of macrophage tumor necrosis factor production by prostaglandin E2. Biochem Biophys Res Commun. 1986 May 29;137(1):404–410. doi: 10.1016/0006-291x(86)91224-6. [DOI] [PubMed] [Google Scholar]
  18. Le J., Vilcek J. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest. 1987 Mar;56(3):234–248. [PubMed] [Google Scholar]
  19. Leizer T., Clarris B. J., Ash P. E., van Damme J., Saklatvala J., Hamilton J. A. Interleukin-1 beta and interleukin-1 alpha stimulate the plasminogen activator activity and prostaglandin E2 levels of human synovial cells. Arthritis Rheum. 1987 May;30(5):562–566. doi: 10.1002/art.1780300511. [DOI] [PubMed] [Google Scholar]
  20. Maury C. P., Teppo A. M. Raised serum levels of cachectin/tumor necrosis factor alpha in renal allograft rejection. J Exp Med. 1987 Oct 1;166(4):1132–1137. doi: 10.1084/jem.166.4.1132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nedwin G. E., Svedersky L. P., Bringman T. S., Palladino M. A., Jr, Goeddel D. V. Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta. J Immunol. 1985 Oct;135(4):2492–2497. [PubMed] [Google Scholar]
  22. Newton R. C. Effect of interferon on the induction of human monocyte secretion of interleukin-1 activity. Immunology. 1985 Nov;56(3):441–449. [PMC free article] [PubMed] [Google Scholar]
  23. Nichols F. C., Garrison S. W. Interferon-gamma potentiation of lipopolysaccharide-induced eicosanoid release from human monocytes. J Interferon Res. 1987 Feb;7(1):121–129. doi: 10.1089/jir.1987.7.121. [DOI] [PubMed] [Google Scholar]
  24. Norton J. M., Munck A. Glucose transport in murine macrophages: in vitro characterization of the monosaccharide transport system of the thioglycollate-elicited mouse peritoneal macrophage. J Immunol. 1980 Jul;125(1):252–258. [PubMed] [Google Scholar]
  25. Rook G. A., Taverne J., Leveton C., Steele J. The role of gamma-interferon, vitamin D3 metabolites and tumour necrosis factor in the pathogenesis of tuberculosis. Immunology. 1987 Oct;62(2):229–234. [PMC free article] [PubMed] [Google Scholar]
  26. Rosenwasser L. J., Dinarello C. A. Ability of human leukocytic pyrogen to enhance phytohemagglutinin induced murine thymocyte proliferation. Cell Immunol. 1981 Sep 1;63(1):134–142. doi: 10.1016/0008-8749(81)90034-4. [DOI] [PubMed] [Google Scholar]
  27. Seckinger P., Isaaz S., Dayer J. M. A human inhibitor of tumor necrosis factor alpha. J Exp Med. 1988 Apr 1;167(4):1511–1516. doi: 10.1084/jem.167.4.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Singer I. I., Scott S., Hall G. L., Limjuco G., Chin J., Schmidt J. A. Interleukin 1 beta is localized in the cytoplasmic ground substance but is largely absent from the Golgi apparatus and plasma membranes of stimulated human monocytes. J Exp Med. 1988 Feb 1;167(2):389–407. doi: 10.1084/jem.167.2.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tsujimoto M., Yip Y. K., Vilcek J. Interferon-gamma enhances expression of cellular receptors for tumor necrosis factor. J Immunol. 1986 Apr 1;136(7):2441–2444. [PubMed] [Google Scholar]
  30. Tweardy D. J., Fujiwara H., Scillian J. J., Ellner J. J. Concurrent enhancement of monocyte immunoregulatory properties and effector functions by recombinant interferon-gamma. Cell Immunol. 1986 Jun;100(1):34–46. doi: 10.1016/0008-8749(86)90004-3. [DOI] [PubMed] [Google Scholar]

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