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. 1990 Jan;61(1):9–13. doi: 10.1038/bjc.1990.4

The effect of adrenalectomy and dexamethasone on interleukin-1 alpha induced responses in RIF-1 tumours.

P G Braunschweiger 1, C S Johnson 1, N Kumar 1, V Ord 1, P Furmanski 1
PMCID: PMC1971311  PMID: 2297494

Abstract

In the present studies the effect of bilateral adrenalectomy on the pathophysiologic responses to recombinant human interleukin-1 alpha (rHIL-1 alpha) was determined in RIF-1 tumour models. Acute vascular injury and haemorrhagic responses were quantitated by the intra-tumour accumulation of 59Fe radiolabelled erythrocytes. In vivo clonogenic tumour cell kill was determined by an excision assay. A single, intraperitoneal rHIL-1 alpha treatment (6.25 x 10(7) D10 units kg-1, 25 micrograms kg-1) resulted in acute tumour haemorrhage and approximately 55% clonogenic tumour cell kill (24 h). Bilateral adrenalectomy, 24 h before rHIL-1 alpha, significantly increased haemorrhagic responses, but haemodynamic toxicity was severe. This toxicity could be ameliorated by giving dexamethasone (5 mg kg-1) before or up to 3 h after rHIL-1 alpha. The effect of dexamethasone on rHIL-1 alpha induced tumour responses in adrenalectomised mice was sequence dependent. Given before rHIL-1 alpha, dexamethasone inhibited tumour haemorrhage. When dexamethasone was given up to 3 h after rHIL-1 alpha, tumour haemorrhage was directly related to sequence interval. Although adrenalectomy and dexamethasone alone had little effect on RIF-1 tumours, adrenalectomy increased rHIL-1 alpha mediated clonogenic tumour cell kill. The surviving fraction 24 h after rHIL-1 alpha (6.25 x 10(7) D10 units kg-1, 25 micrograms kg-1) and dexamethasone (5 mg kg-1, 2 h after rHIL-1 alpha) was 1.3 +/- 0.4%. The surviving fraction after this combination in intact mice (36.7 +/- 1.4%) was approximately 30-fold higher than that seen in adrenalectomised mice. The results indicate that adrenal responses secondary to rHIL-1 alpha treatment exert a negative feedback on rHIL-1 alpha mediated responses in solid tumours.

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Selected References

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

  1. ALPEN E. L., CRANMORE D. Cellular kinetics and iron utilization in bone marrow as observed by Fe59 radioautography. Ann N Y Acad Sci. 1959 Jun 25;77:753–765. doi: 10.1111/j.1749-6632.1959.tb36938.x. [DOI] [PubMed] [Google Scholar]
  2. Bernheim H. A. Is prostaglandin E2 involved in the pathogenesis of fever? Effects of interleukin-1 on the release of prostaglandins. Yale J Biol Med. 1986 Mar-Apr;59(2):151–158. [PMC free article] [PubMed] [Google Scholar]
  3. Bertini R., Bianchi M., Ghezzi P. Adrenalectomy sensitizes mice to the lethal effects of interleukin 1 and tumor necrosis factor. J Exp Med. 1988 May 1;167(5):1708–1712. doi: 10.1084/jem.167.5.1708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Besedovsky H., Sorkin E., Keller M., Müller J. Changes in blood hormone levels during the immune response. Proc Soc Exp Biol Med. 1975 Nov;150(2):466–470. doi: 10.3181/00379727-150-39057. [DOI] [PubMed] [Google Scholar]
  5. Besedovsky H., del Rey A., Sorkin E., Dinarello C. A. Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones. Science. 1986 Aug 8;233(4764):652–654. doi: 10.1126/science.3014662. [DOI] [PubMed] [Google Scholar]
  6. Bevilacqua M. P., Pober J. S., Majeau G. R., Fiers W., Cotran R. S., Gimbrone M. A., Jr Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4533–4537. doi: 10.1073/pnas.83.12.4533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bevilacqua M. P., Pober J. S., Wheeler M. E., Cotran R. S., Gimbrone M. A., Jr Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest. 1985 Nov;76(5):2003–2011. doi: 10.1172/JCI112200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Braunschweiger P. G., Johnson C. S., Kumar N., Ord V., Furmanski P. Antitumor effects of recombinant human interleukin 1 alpha in RIF-1 and Panc02 solid tumors. Cancer Res. 1988 Nov 1;48(21):6011–6016. [PubMed] [Google Scholar]
  9. Braunschweiger P. G., Schiffer L. M. Effect of dexamethasone on vascular function in RIF-1 tumors. Cancer Res. 1986 Jul;46(7):3299–3303. [PubMed] [Google Scholar]
  10. Braunschweiger P. G., Ting H. L., Schiffer L. M. Receptor-dependent antiproliferative effects of corticosteroids in radiation-induced fibrosarcomas and implications for sequential therapy. Cancer Res. 1982 May;42(5):1686–1691. [PubMed] [Google Scholar]
  11. Braunschweiger P. G., Ting H. L., Schiffer L. M. Role of corticosteroid hormones in the control of cell proliferation in residual tumor after surgical cytoreduction. Cancer Res. 1983 Dec;43(12 Pt 1):5801–5807. [PubMed] [Google Scholar]
  12. Del Rey A., Besedovsky H., Sorkin E., Dinarello C. A. Interleukin-1 and glucocorticoid hormones integrate an immunoregulatory feedback circuit. Ann N Y Acad Sci. 1987;496:85–90. doi: 10.1111/j.1749-6632.1987.tb35749.x. [DOI] [PubMed] [Google Scholar]
  13. Dinarello C. A., Marnoy S. O., Rosenwasser L. J. Role of arachidonate metabolism in the immunoregulatory function of human leukocytic pyrogen/lymphocyte-activating factor/interleukin 1. J Immunol. 1983 Feb;130(2):890–895. [PubMed] [Google Scholar]
  14. EBERT R. H., BARCLAY W. R. [Changes in connective tissue reaction induced by cortisone]. Ann Intern Med. 1952 Sep;37(3):506–518. doi: 10.7326/0003-4819-37-3-506. [DOI] [PubMed] [Google Scholar]
  15. Gatti G., Cavallo R., Sartori M. L., Marinone C., Angeli A. Cortisol at physiological concentrations and prostaglandin E2 are additive inhibitors of human natural killer cell activity. Immunopharmacology. 1986 Apr;11(2):119–128. doi: 10.1016/0162-3109(86)90032-9. [DOI] [PubMed] [Google Scholar]
  16. Gillis S., Crabtree G. R., Smith K. A. Glucocorticoid-induced inhibition of T cell growth factor production. I. The effect on mitogen-induced lymphocyte proliferation. J Immunol. 1979 Oct;123(4):1624–1631. [PubMed] [Google Scholar]
  17. Havell E. A., Fiers W., North R. J. The antitumor function of tumor necrosis factor (TNF), I. Therapeutic action of TNF against an established murine sarcoma is indirect, immunologically dependent, and limited by severe toxicity. J Exp Med. 1988 Mar 1;167(3):1067–1085. doi: 10.1084/jem.167.3.1067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Holbrook N. J., Cox W. I., Horner H. C. Direct suppression of natural killer activity in human peripheral blood leukocyte cultures by glucocorticoids and its modulation by interferon. Cancer Res. 1983 Sep;43(9):4019–4025. [PubMed] [Google Scholar]
  19. Issekutz A. C., Movat H. Z. The effect of vasodilator prostaglandins on polymorphonuclear leukocyte infiltration and vascular injury. Am J Pathol. 1982 Jun;107(3):300–309. [PMC free article] [PubMed] [Google Scholar]
  20. Johnson C. S., Keckler D. J., Topper M. I., Braunschweiger P. G., Furmanski P. In vivo hematopoietic effects of recombinant interleukin-1 alpha in mice: stimulation of granulocytic, monocytic, megakaryocytic, and early erythroid progenitors, suppression of late-stage erythropoiesis, and reversal of erythroid suppression with erythropoietin. Blood. 1989 Feb 15;73(3):678–683. [PubMed] [Google Scholar]
  21. Kuehl F. A., Jr, Egan R. W. Prostaglandins, arachidonic acid, and inflammation. Science. 1980 Nov 28;210(4473):978–984. doi: 10.1126/science.6254151. [DOI] [PubMed] [Google Scholar]
  22. Lachman L. B., Dinarello C. A., Llansa N. D., Fidler I. J. Natural and recombinant human interleukin 1-beta is cytotoxic for human melanoma cells. J Immunol. 1986 Apr 15;136(8):3098–3102. [PubMed] [Google Scholar]
  23. Last-Barney K., Homon C. A., Faanes R. B., Merluzzi V. J. Synergistic and overlapping activities of tumor necrosis factor-alpha and IL-1. J Immunol. 1988 Jul 15;141(2):527–530. [PubMed] [Google Scholar]
  24. Letts L. G., Cirino M. Vascular actions of leukotrienes. Prog Clin Biol Res. 1985;199:47–58. [PubMed] [Google Scholar]
  25. Lewis G. D., Campbell W. B., Johnson A. R. Inhibition of prostaglandin synthesis by glucocorticoids in human endothelial cells. Endocrinology. 1986 Jul;119(1):62–69. doi: 10.1210/endo-119-1-62. [DOI] [PubMed] [Google Scholar]
  26. MacGregor R. R. The effect of anti-inflammatory agents and inflammation on granulocyte adherence. Evidence for regulation by plasma factors. Am J Med. 1976 Nov;61(5):597–607. doi: 10.1016/0002-9343(76)90137-6. [DOI] [PubMed] [Google Scholar]
  27. Maca R. D., Fry G. L., Hakes A. D. Effects of glucocorticoids on the interaction of lymphoblastoid cells with human endothelial cells in vitro. Cancer Res. 1978 Aug;38(8):2224–2228. [PubMed] [Google Scholar]
  28. Morrissey P. J., Charrier K., Alpert A., Bressler L. In vivo administration of IL-1 induces thymic hypoplasia and increased levels of serum corticosterone. J Immunol. 1988 Sep 1;141(5):1456–1463. [PubMed] [Google Scholar]
  29. Nachman R. L., Hajjar K. A., Silverstein R. L., Dinarello C. A. Interleukin 1 induces endothelial cell synthesis of plasminogen activator inhibitor. J Exp Med. 1986 Jun 1;163(6):1595–1600. doi: 10.1084/jem.163.6.1595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Nakamura S., Nakata K., Kashimoto S., Yoshida H., Yamada M. Antitumor effect of recombinant human interleukin 1 alpha against murine syngeneic tumors. Jpn J Cancer Res. 1986 Aug;77(8):767–773. [PubMed] [Google Scholar]
  31. Nakata K., Kashimoto S., Yoshida H., Oku T., Nakamura S. Augmented antitumor effect of recombinant human interleukin-1 alpha by indomethacin. Cancer Res. 1988 Feb 1;48(3):584–588. [PubMed] [Google Scholar]
  32. Ozaki Y., Ohashi T., Kume S. Potentiation of neutrophil function by recombinant DNA-produced interleukin 1a. J Leukoc Biol. 1987 Dec;42(6):621–627. doi: 10.1002/jlb.42.6.621. [DOI] [PubMed] [Google Scholar]
  33. Philip R., Epstein L. B. Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, gamma-interferon and interleukin-1. Nature. 1986 Sep 4;323(6083):86–89. doi: 10.1038/323086a0. [DOI] [PubMed] [Google Scholar]
  34. Ruggiero V., Baglioni C. Synergistic anti-proliferative activity of interleukin 1 and tumor necrosis factor. J Immunol. 1987 Feb 1;138(3):661–663. [PubMed] [Google Scholar]
  35. Samuelsson B. Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science. 1983 May 6;220(4597):568–575. doi: 10.1126/science.6301011. [DOI] [PubMed] [Google Scholar]
  36. Schaffner A. Therapeutic concentrations of glucocorticoids suppress the antimicrobial activity of human macrophages without impairing their responsiveness to gamma interferon. J Clin Invest. 1985 Nov;76(5):1755–1764. doi: 10.1172/JCI112166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Twentyman P. R., Brown J. M., Gray J. W., Franko A. J., Scoles M. A., Kallman R. F. A new mouse tumor model system (RIF-1) for comparison of end-point studies. J Natl Cancer Inst. 1980 Mar;64(3):595–604. [PubMed] [Google Scholar]
  38. Vlassara H., Brownlee M., Manogue K. R., Dinarello C. A., Pasagian A. Cachectin/TNF and IL-1 induced by glucose-modified proteins: role in normal tissue remodeling. Science. 1988 Jun 10;240(4858):1546–1548. doi: 10.1126/science.3259727. [DOI] [PubMed] [Google Scholar]
  39. Watanabe N., Niitsu Y., Umeno H., Kuriyama H., Neda H., Yamauchi N., Maeda M., Urushizaki I. Toxic effect of tumor necrosis factor on tumor vasculature in mice. Cancer Res. 1988 Apr 15;48(8):2179–2183. [PubMed] [Google Scholar]
  40. del Rey A., Besedovsky H., Sorkin E. Endogenous blood levels of corticosterone control the immunologic cell mass and B cell activity in mice. J Immunol. 1984 Aug;133(2):572–575. [PubMed] [Google Scholar]

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