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. 1989 Aug;67(4):514–519.

Tumour necrosis factor production by IL-2-activated macrophages in vitro and in vivo.

J S Economou 1, W H McBride 1, R Essner 1, K Rhoades 1, S Golub 1, E C Holmes 1, D L Morton 1
PMCID: PMC1385323  PMID: 2788610

Abstract

Purified human and murine monocytes can be activated in vitro by human recombinant IL-2 to secrete tumour necrosis factor (TNF). TNF mRNA is detected within 4 h of addition of IL-2. Signal transduction does not appear to require expression of the Tac peptide of the IL-2 receptor. IL-2 does, however, induce Tac mRNA and Tac peptide expression on peripheral blood monocytes (PBM). In addition to these in vitro studies, PBM retrieved from IL-2-treated cancer patients and mice have been shown to have a greatly increased capacity for TNF production. These studies identify a pathway for macrophage activation by IL-2 both in vitro and in vivo. They also suggest a mechanism for some of the immunoregulatory and toxic effects of IL-2 based immunotherapy regimens.

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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., Cerami A. Cachectin: more than a tumor necrosis factor. N Engl J Med. 1987 Feb 12;316(7):379–385. doi: 10.1056/NEJM198702123160705. [DOI] [PubMed] [Google Scholar]
  2. Beutler B., Tkacenko V., Milsark I., Krochin N., Cerami A. Effect of gamma interferon on cachectin expression by mononuclear phagocytes. Reversal of the lpsd (endotoxin resistance) phenotype. J Exp Med. 1986 Nov 1;164(5):1791–1796. doi: 10.1084/jem.164.5.1791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bich-Thuy L. T., Dukovich M., Peffer N. J., Fauci A. S., Kehrl J. H., Greene W. C. Direct activation of human resting T cells by IL 2: the role of an IL 2 receptor distinct from the Tac protein. J Immunol. 1987 Sep 1;139(5):1550–1556. [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Haskill S., Johnson C., Eierman D., Becker S., Warren K. Adherence induces selective mRNA expression of monocyte mediators and proto-oncogenes. J Immunol. 1988 Mar 1;140(5):1690–1694. [PubMed] [Google Scholar]
  7. Lotze M. T., Custer M. C., Sharrow S. O., Rubin L. A., Nelson D. L., Rosenberg S. A. In vivo administration of purified human interleukin-2 to patients with cancer: development of interleukin-2 receptor positive cells and circulating soluble interleukin-2 receptors following interleukin-2 administration. Cancer Res. 1987 Apr 15;47(8):2188–2195. [PubMed] [Google Scholar]
  8. Lotze M. T., Matory Y. L., Rayner A. A., Ettinghausen S. E., Vetto J. T., Seipp C. A., Rosenberg S. A. Clinical effects and toxicity of interleukin-2 in patients with cancer. Cancer. 1986 Dec 15;58(12):2764–2772. doi: 10.1002/1097-0142(19861215)58:12<2764::aid-cncr2820581235>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  9. Malkovský M., Loveland B., North M., Asherson G. L., Gao L., Ward P., Fiers W. Recombinant interleukin-2 directly augments the cytotoxicity of human monocytes. Nature. 1987 Jan 15;325(6101):262–265. doi: 10.1038/325262a0. [DOI] [PubMed] [Google Scholar]
  10. Mulé J. J., Yang J., Shu S., Rosenberg S. A. The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo: direct correlation between reduction of established metastases and cytolytic activity of lymphokine-activated killer cells. J Immunol. 1986 May 15;136(10):3899–3909. [PubMed] [Google Scholar]
  11. 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]
  12. Nikaido T., Shimizu A., Ishida N., Sabe H., Teshigawara K., Maeda M., Uchiyama T., Yodoi J., Honjo T. Molecular cloning of cDNA encoding human interleukin-2 receptor. Nature. 1984 Oct 18;311(5987):631–635. doi: 10.1038/311631a0. [DOI] [PubMed] [Google Scholar]
  13. Old L. J. Tumor necrosis factor (TNF). Science. 1985 Nov 8;230(4726):630–632. doi: 10.1126/science.2413547. [DOI] [PubMed] [Google Scholar]
  14. Pennica D., Nedwin G. E., Hayflick J. S., Seeburg P. H., Derynck R., Palladino M. A., Kohr W. J., Aggarwal B. B., Goeddel D. V. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 1984 Dec 20;312(5996):724–729. doi: 10.1038/312724a0. [DOI] [PubMed] [Google Scholar]
  15. Pober J. S., Bevilacqua M. P., Mendrick D. L., Lapierre L. A., Fiers W., Gimbrone M. A., Jr Two distinct monokines, interleukin 1 and tumor necrosis factor, each independently induce biosynthesis and transient expression of the same antigen on the surface of cultured human vascular endothelial cells. J Immunol. 1986 Mar 1;136(5):1680–1687. [PubMed] [Google Scholar]
  16. Ponte P., Gunning P., Blau H., Kedes L. Human actin genes are single copy for alpha-skeletal and alpha-cardiac actin but multicopy for beta- and gamma-cytoskeletal genes: 3' untranslated regions are isotype specific but are conserved in evolution. Mol Cell Biol. 1983 Oct;3(10):1783–1791. doi: 10.1128/mcb.3.10.1783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Unanue E. R., Allen P. M. The basis for the immunoregulatory role of macrophages and other accessory cells. Science. 1987 May 1;236(4801):551–557. doi: 10.1126/science.2437650. [DOI] [PubMed] [Google Scholar]
  18. Vogel S. N., Douches S. D., Kaufman E. N., Neta R. Induction of colony stimulating factor in vivo by recombinant interleukin 1 alpha and recombinant tumor necrosis factor alpha 1. J Immunol. 1987 Apr 1;138(7):2143–2148. [PubMed] [Google Scholar]
  19. Wahl S. M., McCartney-Francis N., Hunt D. A., Smith P. D., Wahl L. M., Katona I. M. Monocyte interleukin 2 receptor gene expression and interleukin 2 augmentation of microbicidal activity. J Immunol. 1987 Aug 15;139(4):1342–1347. [PubMed] [Google Scholar]

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