Skip to main content

Advertisement

SpringerLink
Log in

Inhibition of prostaglandin E2 formation and histamine action in cancer immunotherapy

  • Original Articles
  • Cancer Immunotherapy, Prostaglandin E2, Histamine, Indomethacin, Cimetidine
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

The activity of cell-mediated defense systems is stimulated by consecutive formation of interleukin-1β (IL-1β), interleukin-2 (IL-2) and interferon γ (IFNγ). The system is inhibited by interleukin-4 (IL-4) and also by prostaglandin E2 (PGE2) and histamine, which are released when the immune system is activated. The inhibition is strong in cancer patients, because PGE2 is formed in many cancer cells and its formation is stimulated by IL-1β. The release of histamine is also stimulated by IL-1β. Tus PGE2 and histamine are feedback inhibitors of cell-mediated immunity. This inhibition can be abolished by inhibitors of the cyclo-oxygenase (e. g. indomethacin) and H-2 receptor antagonists (e. g. cimetidine). This may offer a new option to stimulate the immune system to kill cancer cells.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Akama H, Ickikawa Y, Matsushit Y, Shinozawa T, Homma M (1990) Mononuclear cells enhance prostaglandin E2 production of polymorphonuclear leukocytes via tumor necrosis factor α. Biochem Biophys Res Commun 168: 857

    PubMed  Google Scholar 

  2. Allen JI, Syropoulus HJ, Grant B (1987) Cimetidine modulates natural killer cell function of patients with chronic lymphocytic leukemia. J Lab Clin Med 109: 396

    PubMed  Google Scholar 

  3. Arend WP, Gordon DF, Wood WM, Janson RW, Joslin FG, Jameel S (1989) IL-1β production in cultured human monocytes is regulated at multiple levels. J Immunol 143: 118

    PubMed  Google Scholar 

  4. Armitage JO, Sidner RD (1979) Antitumor effect of cimetidine? Lancet 1: 882

    Google Scholar 

  5. Bray RA, Brahmi Z (1986) Role of lipoxygenation in human natural killer cell activation. J Immunol 136: 1783

    PubMed  Google Scholar 

  6. Brockmeyer NH, Kreuzfelder E, Chalabi N, Scheiermann N, Keinecke HO, Goos M, Ohnhaus EE (1989) The immunomodulatory potency of cimetidine in healthy volunteers. Int J Clin Pharmacol Ther Toxicol 27: 458

    PubMed  Google Scholar 

  7. di Giovine F, Duff GW (1990) Interleukin 1: the first interleukin. Immunol Today 11: 13

    PubMed  Google Scholar 

  8. Dohlsten M (1988) Suppressive effects of histamine on T cell activation. Academic dissertation, University of Lund, Lund

    Google Scholar 

  9. Dohlsten M, Sjögren HO, Carlsson R (1987) Histamine acts directly on human T cells to inhibit interleukin-2 and interferon-γ production. Cell Immunol 109: 65

    PubMed  Google Scholar 

  10. Dohlsten M, Hedlund G, Fischer H, Sjögren HO, Carlsson R (1989) Proliferation of human CD4+45R+ and CD+45R− T helper cells is promoted by both IL-2 and IL-4 while interferon-gamma production is restricted to IL-2 activated CD4+45R− T cells. Immunol Lett 20: 29

    PubMed  Google Scholar 

  11. Donnelly RP, Fenton MJ, Kaufmann JD, Gerrard TL (1991) IL-1 expression in human monocytes is transcriptionally and posttranscriptionally regulated by IL-4. J Immunol 146: 3431

    PubMed  Google Scholar 

  12. Essner R, Rhoades K, McBride WH, Morton DL, Economou JS (1989) IL-4 down-regulates IL-1 and TNF gene expression in human monocytes. J Immunol 142: 3857

    PubMed  Google Scholar 

  13. Falus A, Meretey K (1992) Histamine: an early messenger in inflammatory and immune reactions. Immunol Today 13: 154

    PubMed  Google Scholar 

  14. Fischer H, Hedlund G, Kalland T, Sjögren HO, Dohlsten M (1990) Independent regulation of IFN-γ and tumor necrosis factor by IL-1 in human T helper cells. J Immunol 145: 3767

    PubMed  Google Scholar 

  15. Garcia-Penarrubia P, Bankhurst AD, Koster FT (1989) Prostaglandins from human T suppressor/cytotoxic cells modulate natural killer antibacterial activity. J Exp Med 170: 601

    PubMed  Google Scholar 

  16. Goodwin JS (1985) Immunologic effects of nonsteroidal anti-inflammatory drugs. Med Clin North Am 69: 793

    PubMed  Google Scholar 

  17. Goodwin JS, Kaszubowski PA, Williams RC Jr (1979) Cyclic adenosine monophosphate response to prostaglandin E2 in subpopulations of human lymphocytes. J Exp Med 150: 1260

    PubMed  Google Scholar 

  18. Goto T, Herberman RB, Maluish A, Strong DM (1983) Cyclic AMP as a mediator of prostaglandin E-induced suppression of human natural killer cell activity. J Immunol 130: 1350

    PubMed  Google Scholar 

  19. Hart PH, Vitti GF, Burgess DR, Whitty GA, Piccoli DS, Hamilton JA (1989) Potential antiinflammatory effects of interleukin 4: suppression of human monocyte tumor necrosis factor α, interleukin 1, and prostaglandin E2. Proc Natl Acad Sci USA 86: 3803

    PubMed  Google Scholar 

  20. Hart PH, Whitty GA, Piccoli DS, Hamilton JA (1989) Control by IFN-γ and PGE2 of TNFα and IL-1 production by human monocytes. Immunology 66: 376

    PubMed  Google Scholar 

  21. Hellstrand K, Hermodsson S (1987) Differential effects of histamine receptor antagonists on human natural killer cell activity. Int Arch Allergy Appl Immunol 84: 247

    PubMed  Google Scholar 

  22. Hellstrand K, Hermodsson S (1990) A cell-to-cell mediated interaction involving monocytes and non-T/CD 16+ natural killer (NK) cells is required for histamine H2-receptor-mediated NK-cell activation. Scand J Immunol 31: 631

    PubMed  Google Scholar 

  23. Hellstrand K, Asea A, Hermodsson S (1990) Role of histamine in natural killer cell-mediated resistance against tumor cells. J Immunol 145: 4365

    PubMed  Google Scholar 

  24. Hotermans G, Bury T, Radermecker MF (1991) Effect of histamine on tumor necrosis factor production by human monocytes. Int J Allergy Appl Immunol 95: 278

    Google Scholar 

  25. Ijzermans JNM, Marquet RL (1989) Interferon-gamma: a review. Immunobiology 179: 456

    PubMed  Google Scholar 

  26. Kärre K, Hansson M, Kiessling R (1991) Multiple interactions at the natural killer workshop. Immunol Today 12: 343

    PubMed  Google Scholar 

  27. Kaplan AP, Reddigari S, Baeza M, Kuna P (1991) Histamine releasing factors and cytokine-dependent activation of basophils and mast cells. Adv Immunol 50: 237

    PubMed  Google Scholar 

  28. Khan MM, Sansoni P, Engleman EG, Melmon KL (1985) Pharmacologic effects of autacoids on subsets of T cells. J Clin Invest 75: 1578

    PubMed  Google Scholar 

  29. Koren HS, Anderson SJ, Fischer DG, Copeland CS, Jensen PJ (1981) Regulation of human natural killing. I. The role of monocytes, interferon, and prostaglandins. J Immunol 127: 2007

    PubMed  Google Scholar 

  30. Krause DS, Deutsch C (1991) Cyclic AMP directly inhibits IL-2 receptor expression in human T cells: expression of both p55 and p75 subunits is affected. J Immunol 146: 2285

    PubMed  Google Scholar 

  31. Kuna P, Reddigari SR, Kornfeld D, Kaplan AP (1991) IL-8 inhibits histamine release from human basophils induced by histamine-releasing factors, connetive tissue activating peptide III, and IL-3. J Immunol 147: 1920

    PubMed  Google Scholar 

  32. Kunkel IL, Spengler M, May MA, Spengler R, Larrick J, Remick D (1988) Prostaglandin E2 regulates macrophage-derived tumor necrosis factor. J Biol Chem 263: 5380

    PubMed  Google Scholar 

  33. Last-Barney K, Homon CA, Faanes RB, Merluzzi VJ (1988) Synergistic and overlapping activities of tumor necrosis factor-α and IL-1. J Immunol 141: 527

    PubMed  Google Scholar 

  34. Mary D, Aussel C, Ferrua B, Fehlmann M (1987) Regulation of interleukin 2 synthesis by cAMP in human T cells. J Immunol 139: 1179

    PubMed  Google Scholar 

  35. Merluzzi VJ, Faanes RB, Czajkowski M, Last-Barney K, Harrison PC, Kahn J, Rothlein R (1987) Membrane-associated interleukin 1 activity on human U937 tumor cells: stimulation of PGE2 production by human chondrosarcoma cells. J Immunol 139: 166

    PubMed  Google Scholar 

  36. Mertens WC, Bramwell VHC, Gwadry-Sridhar F, Romano W, Banerjee D, Lala PK (1992) Effect of indomethacin plus ranitidine in advanced melanoma patients on high-dose interleukin-2. Lancet 340: 397

    PubMed  Google Scholar 

  37. Meyer JD, Yurt RW, Duhaney R, Hesse DG, Tracey KJ, Fong Y, Verma M, Shires GT, Dineen P, Lowry SF, Davis JM (1988) Tumor necrosis factor—enhanced leukotriene B4 generation and chemotaxis in human neutrophils. Arch Surg 123: 1454

    PubMed  Google Scholar 

  38. Mizel SB (1989) The interleukins. FASEB J 3: 2379

    PubMed  Google Scholar 

  39. Moxey-Mims MM, Simms HH, Frank MM, Lin EY, Gaither TA (1991) The effects of IL-1, IL-2, and tumor-necrosis factor on polymorphonuclear leukocyte Fcy receptor-mediated phagocytosis. J Immunol 147: 1823

    PubMed  Google Scholar 

  40. Newton RC (1985) Effect of interferon on the induction of human monocyte secretion of interleukin-1 activity. Immunology 56: 441

    PubMed  Google Scholar 

  41. Pene J, Rousset F, Briere F, Chretien I, Paliard X, Banchereau J, Spits H, De Vries JE (1988) IgE production by normal human B cells induced by alloreactive T cell clones is mediated by IL-4 and suppressed by IFN-γ. J Immunol 141: 1218

    PubMed  Google Scholar 

  42. Phipps RP, Stein SH, Roper RL (1991) A new view of prostaglandin E regulation of the immune response. Immunol Today 12: 349

    PubMed  Google Scholar 

  43. Ramstedt U, Ng J, Wigzell H, Serhan CN, Samuelsson B (1985) Action of novel eicosanoids lipoxin A and B on human natural killer cell cytotoxicity: effects on intracellular cAMP and target cell binding. J Immunol 135: 3434

    PubMed  Google Scholar 

  44. Rappaport RS, Dodge GR (1982) Prostaglandin E inhibits the production of human interleukin 2. J Exp Med 155: 943

    PubMed  Google Scholar 

  45. Rincon M, Tugores A, Lopez-Rivas A, Silva A, Alonso M, De Landazuri MO Lopez-Botet M (1988) Prostaglandin E2 and the increase of intracellular cAMP inhibits the expression of interleukin-2 receptors in human T cells. Eur J Immunol 18: 1791

    PubMed  Google Scholar 

  46. Rola-Pleszczynski M, Gagnon L, Sirois P (1983) Leukotriene B4 augments human natural cytotoxic cell activity. Biochem Biophys Res Commun 113: 531

    PubMed  Google Scholar 

  47. Samuelsson B (1983) Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science 220: 568

    PubMed  Google Scholar 

  48. Schröder J-M (1989) The monocyte-derived neutrophil activating peptide (NAP/interleukin 8) stimulates human neutrophil arachidonate-5-lipoxygenase, but not the release of cellular arachidonate. J Exp Med 170: 847

    PubMed  Google Scholar 

  49. Smith KA (1990) Interleukin-2. Sci Am 262: 50

    PubMed  Google Scholar 

  50. Smith TJ, Kaplowitz LG (1991) Pilot study of cimetidine in the treatment of Kaposi's sarcoma in patients with acquired immunodeficiency syndrome. JNCI 83: 139

    PubMed  Google Scholar 

  51. Standiford TJ, Strieter RM, Chensue SW, Westwick J, Kasahara K, Kunkel SL (1990) IL-4 inhibits the expression of IL-8 from stimulated human monocytes. J Immunol 145: 1435

    PubMed  Google Scholar 

  52. Strieter RM, Chensue SW, Standiford TJ, Basha MA, Showell HJ, Kunkel SL (1990) Disparate gene expression of chemotactic cytokines by human mononuclear phagocytes. Biochem Biophys Res Commun 166: 886

    PubMed  Google Scholar 

  53. Strieter RM, Remick DG, Ham JM, Colletti LM, Lynch JP, Kunkel SL (1990) Tumor necrosis factor-alpha gene expression in human blood. J Leukoc Biol 47: 366

    PubMed  Google Scholar 

  54. Subramanian N, Bray MA (1987) Interleukin 1 releases histamine from human basophils and mast cells in vitro. J Immunol 138: 271

    PubMed  Google Scholar 

  55. Topley N, Floege J, Wessel K, Hass R, Radeke HH, Kaever V, Resch K (1989) Prostaglandin E2 production is synergistically increased in cultured human glomerular mesangial cells by combinations of IL-1 and tumor necrosis factor-α. J Immunol 143: 1989

    PubMed  Google Scholar 

  56. Uotila P, Vapaatalo H (1984) Synthesis, pathways and biological implications of eicosanoids. Ann Clin Res 16: 226

    PubMed  Google Scholar 

  57. Walker C, Kristensen F, Bettens F, de Weck AL (1983) Lymphokine regulation of activated (G1) lymphocytes. I. Prostaglandin E2-induced inhibition of interleukin 2 production. J Immunol 130: 1770

    PubMed  Google Scholar 

  58. Yang J, Zucker-Franklin D (1984) Modulation of natural killer (NK) cells by autologous neutrophils and monocytes. Cell Immunol 86: 171

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, University of Turku, Kiinamyllynkatu 10, SF-20520, Turku, Finland

    Pekka Uotila

Authors
  1. Pekka Uotila
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Uotila, P. Inhibition of prostaglandin E2 formation and histamine action in cancer immunotherapy. Cancer Immunol Immunother 37, 251–254 (1993). https://doi.org/10.1007/BF01518519

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01518519

Key words

Search

Navigation