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. 1989 May;86(10):3803–3807. doi: 10.1073/pnas.86.10.3803

Potential antiinflammatory effects of interleukin 4: suppression of human monocyte tumor necrosis factor alpha, interleukin 1, and prostaglandin E2.

P H Hart 1, G F Vitti 1, D R Burgess 1, G A Whitty 1, D S Piccoli 1, J A Hamilton 1
PMCID: PMC287229  PMID: 2786204

Abstract

Stimulated human monocytes/macrophages are a source of mediators such as tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), and prostaglandin E2 (PGE2), which can modulate inflammatory and immune reactions. Therefore, the ability to control the production of such mediators by monocytes/macrophages may have therapeutic benefits, and it has been proposed that glucocorticoids may act in this way. Purified human monocytes, when stimulated in vitro with lipopolysaccharide (LPS) or with LPS and gamma interferon (IFN-gamma), produce TNF-alpha, IL-1, and PGE2. Cotreatment of stimulated cells with the purified human lymphokine, interleukin 4 (IL-4 greater than or equal to 0.1-0.5 unit/ml; 12-60 pM) dramatically blocked the increased levels of these three mediators; for TNF-alpha and IL-1, the inhibition was manifest at the level of mRNA. Thus, IL-4 can suppress some parameters of monocyte activation and, as for B cells, have opposite effects to IFN-gamma. The effects of IL-4 on human monocytes are similar to those obtained with the glucocorticoid dexamethasone (0.1 microM).

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Selected References

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

  1. Beutler B., Krochin N., Milsark I. W., Luedke C., Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science. 1986 May 23;232(4753):977–980. doi: 10.1126/science.3754653. [DOI] [PubMed] [Google Scholar]
  2. Cahill J., Hopper K. E. Immunoregulation by macrophages. III. Prostaglandin E suppresses lymphocyte activation but not macrophage effector function during Salmonella enteritidis infection. Int J Immunopharmacol. 1984;6(1):9–17. doi: 10.1016/0192-0561(84)90029-8. [DOI] [PubMed] [Google Scholar]
  3. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  4. Crawford R. M., Finbloom D. S., Ohara J., Paul W. E., Meltzer M. S. B cell stimulatory factor-1 (interleukin 4) activates macrophages for increased tumoricidal activity and expression of Ia antigens. J Immunol. 1987 Jul 1;139(1):135–141. [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Dinarello C. A. The biology of interleukin 1 and comparison to tumor necrosis factor. Immunol Lett. 1987 Dec;16(3-4):227–231. doi: 10.1016/0165-2478(87)90151-9. [DOI] [PubMed] [Google Scholar]
  8. Flower R. J., Blackwell G. J. Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation. Nature. 1979 Mar 29;278(5703):456–459. doi: 10.1038/278456a0. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Hamilton J. A., Slywka J. Stimulation of human synovial fibroblast plasminogen activator production by mononuclear cell supernatants. J Immunol. 1981 Mar;126(3):851–855. [PubMed] [Google Scholar]
  11. Hart P. H., Whitty G. A., Piccoli D. S., Hamilton J. A. Control by IFN-gamma and PGE2 of TNF alpha and IL-1 production by human monocytes. Immunology. 1989 Mar;66(3):376–383. [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Howard M., Farrar J., Hilfiker M., Johnson B., Takatsu K., Hamaoka T., Paul W. E. Identification of a T cell-derived b cell growth factor distinct from interleukin 2. J Exp Med. 1982 Mar 1;155(3):914–923. doi: 10.1084/jem.155.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jelinek D. F., Lipsky P. E. Inhibitory influence of IL-4 on human B cell responsiveness. J Immunol. 1988 Jul 1;141(1):164–173. [PubMed] [Google Scholar]
  15. Kelso A., Gough N. M. Coexpression of granulocyte-macrophage colony-stimulating factor, gamma interferon, and interleukins 3 and 4 is random in murine alloreactive T-lymphocyte clones. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9189–9193. doi: 10.1073/pnas.85.23.9189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kenney J. S., Masada M. P., Eugui E. M., Delustro B. M., Mulkins M. A., Allison A. C. Monoclonal antibodies to human recombinant interleukin 1 (IL 1)beta: quantitation of IL 1 beta and inhibition of biological activity. J Immunol. 1987 Jun 15;138(12):4236–4242. [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. Lee S. W., Tsou A. P., Chan H., Thomas J., Petrie K., Eugui E. M., Allison A. C. Glucocorticoids selectively inhibit the transcription of the interleukin 1 beta gene and decrease the stability of interleukin 1 beta mRNA. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1204–1208. doi: 10.1073/pnas.85.4.1204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. O'Garra A., Umland S., De France T., Christiansen J. 'B-cell factors' are pleiotropic. Immunol Today. 1988 Feb;9(2):45–54. doi: 10.1016/0167-5699(88)91259-5. [DOI] [PubMed] [Google Scholar]
  22. Paul W. E., Ohara J. B-cell stimulatory factor-1/interleukin 4. Annu Rev Immunol. 1987;5:429–459. doi: 10.1146/annurev.iy.05.040187.002241. [DOI] [PubMed] [Google Scholar]
  23. Ralph P., Nakoinz I., Rennick D. Role of interleukin 2, interleukin 4, and alpha, beta, and gamma interferon in stimulating macrophage antibody-dependent tumoricidal activity. J Exp Med. 1988 Feb 1;167(2):712–717. doi: 10.1084/jem.167.2.712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rousset F., Malefijt R. W., Slierendregt B., Aubry J. P., Bonnefoy J. Y., Defrance T., Banchereau J., de Vries J. E. Regulation of Fc receptor for IgE (CD23) and class II MHC antigen expression on Burkitt's lymphoma cell lines by human IL-4 and IFN-gamma. J Immunol. 1988 Apr 15;140(8):2625–2632. [PubMed] [Google Scholar]
  25. Saklatvala J. Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature. 1986 Aug 7;322(6079):547–549. doi: 10.1038/322547a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Stenson W. F., Parker C. W. Prostaglandins, macrophages, and immunity. J Immunol. 1980 Jul;125(1):1–5. [PubMed] [Google Scholar]
  27. Stuart P. M., Zlotnik A., Woodward J. G. Induction of class I and class II MHC antigen expression on murine bone marrow-derived macrophages by IL-4 (B cell stimulatory factor 1). J Immunol. 1988 Mar 1;140(5):1542–1547. [PubMed] [Google Scholar]
  28. Vercelli D., Jabara H. H., Lee B. W., Woodland N., Geha R. S., Leung D. Y. Human recombinant interleukin 4 induces Fc epsilon R2/CD23 on normal human monocytes. J Exp Med. 1988 Apr 1;167(4):1406–1416. doi: 10.1084/jem.167.4.1406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Vitti G., Hamilton J. A. Modulation of urokinase-type plasminogen activator messenger RNA levels in human synovial fibroblasts by interleukin-1, retinoic acid, and a glucocorticoid. Arthritis Rheum. 1988 Aug;31(8):1046–1051. doi: 10.1002/art.1780310817. [DOI] [PubMed] [Google Scholar]
  30. Yokota T., Otsuka T., Mosmann T., Banchereau J., DeFrance T., Blanchard D., De Vries J. E., Lee F., Arai K. Isolation and characterization of a human interleukin cDNA clone, homologous to mouse B-cell stimulatory factor 1, that expresses B-cell- and T-cell-stimulating activities. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5894–5898. doi: 10.1073/pnas.83.16.5894. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. te Velde A. A., Klomp J. P., Yard B. A., de Vries J. E., Figdor C. G. Modulation of phenotypic and functional properties of human peripheral blood monocytes by IL-4. J Immunol. 1988 Mar 1;140(5):1548–1554. [PubMed] [Google Scholar]

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