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. 1989 Jan;65(1):80–92.

Interleukin-1 and the effects of cyclooxygenase inhibitors on its biological activities.

C A Dinarello
PMCID: PMC1807787  PMID: 2513997

Abstract

Interleukin-1 (IL-1) is a polypeptide produced following infection, injury, or antigenic challenge. Although the macrophage is a primary source of IL-1, epidermal, epithelial, lymphoid, and vascular tissues synthesize IL-1. When IL-1 gains access to the circulation, it induces a broad spectrum of systemic changes in physiologic, neurologic, metabolic, hematologic, and endocrine systems. However, because IL-1 lacks a signal peptide, a considerable amount of the IL-1 synthesized may remain associated with the cell and particularly as part of the plasma membrane where it may participate in lymphocyte activation and mesenchymal tissue remodeling. Two gene products code for IL-1: IL-1-beta and IL-1-alpha. The spectrum of biological activities of IL-1 are induced by both forms and receptors for IL-1 recognize both forms. The most consistent property of IL-1 is upregulation of cellular metabolism and increased expression of several genes coding for biologically active molecules. IL-1 is a highly inflammatory molecule and stimulates the production of arachidonic acid metabolites, most consistently, prostaglandin E. IL-1 also acts synergistically with other cytokines, particularly tumor necrosis factor. Some of the multiple biological effects of IL-1 and tumor necrosis factor are prevented by cyclooxygenase inhibitors whereas others are unaffected. Given the widespread use of cyclooxygenase inhibitors, understanding their effect on IL-1 and tumor necrosis factor action is important in several disease models.

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Selected References

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  1. ATKINS E. Pathogenesis of fever. Physiol Rev. 1960 Jul;40:580–646. doi: 10.1152/physrev.1960.40.3.580. [DOI] [PubMed] [Google Scholar]
  2. Antoni G., Presentini R., Perin F., Tagliabue A., Ghiara P., Censini S., Volpini G., Villa L., Boraschi D. A short synthetic peptide fragment of human interleukin 1 with immunostimulatory but not inflammatory activity. J Immunol. 1986 Nov 15;137(10):3201–3204. [PubMed] [Google Scholar]
  3. Auron P. E., Webb A. C., Rosenwasser L. J., Mucci S. F., Rich A., Wolff S. M., Dinarello C. A. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7907–7911. doi: 10.1073/pnas.81.24.7907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bakouche O., Brown D. C., Lachman L. B. Subcellular localization of human monocyte interleukin 1: evidence for an inactive precursor molecule and a possible mechanism for IL 1 release. J Immunol. 1987 Jun 15;138(12):4249–4255. [PubMed] [Google Scholar]
  5. Balavoine J. F., de Rochemonteix B., Williamson K., Seckinger P., Cruchaud A., Dayer J. M. Prostaglandin E2 and collagenase production by fibroblasts and synovial cells is regulated by urine-derived human interleukin 1 and inhibitor(s). J Clin Invest. 1986 Oct;78(4):1120–1124. doi: 10.1172/JCI112669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Beuscher H. U., Fallon R. J., Colten H. R. Macrophage membrane interleukin 1 regulates the expression of acute phase proteins in human hepatoma Hep 3B cells. J Immunol. 1987 Sep 15;139(6):1896–1901. [PubMed] [Google Scholar]
  7. Bird T. A., Saklatvala J. Studies on the fate of receptor-bound 125I-interleukin 1 beta in porcine synovial fibroblasts. J Immunol. 1987 Jul 1;139(1):92–97. [PubMed] [Google Scholar]
  8. Brown K. M., Muchmore A. V., Rosenstreich D. L. Uromodulin, an immunosuppressive protein derived from pregnancy urine, is an inhibitor of interleukin 1. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9119–9123. doi: 10.1073/pnas.83.23.9119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Clark B. D., Collins K. L., Gandy M. S., Webb A. C., Auron P. E. Genomic sequence for human prointerleukin 1 beta: possible evolution from a reverse transcribed prointerleukin 1 alpha gene. Nucleic Acids Res. 1986 Oct 24;14(20):7897–7914. doi: 10.1093/nar/14.20.7897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dinarello C. A., Clowes G. H., Jr, Gordon A. H., Saravis C. A., Wolff S. M. Cleavage of human interleukin 1: isolation of a peptide fragment from plasma of febrile humans and activated monocytes. J Immunol. 1984 Sep;133(3):1332–1338. [PubMed] [Google Scholar]
  11. Dinarello C. A., Clowes G. H., Jr, Gordon A. H., Saravis C. A., Wolff S. M. Cleavage of human interleukin 1: isolation of a peptide fragment from plasma of febrile humans and activated monocytes. J Immunol. 1984 Sep;133(3):1332–1338. [PubMed] [Google Scholar]
  12. Dinarello C. A., Ikejima T., Warner S. J., Orencole S. F., Lonnemann G., Cannon J. G., Libby P. Interleukin 1 induces interleukin 1. I. Induction of circulating interleukin 1 in rabbits in vivo and in human mononuclear cells in vitro. J Immunol. 1987 Sep 15;139(6):1902–1910. [PubMed] [Google Scholar]
  13. Dinarello C. A. Interleukin-1. Rev Infect Dis. 1984 Jan-Feb;6(1):51–95. doi: 10.1093/clinids/6.1.51. [DOI] [PubMed] [Google Scholar]
  14. Dinarello C. A., Renfer L., Wolff S. M. Human leukocytic pyrogen: purification and development of a radioimmunoassay. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4624–4627. doi: 10.1073/pnas.74.10.4624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fenton M. J., Clark B. D., Collins K. L., Webb A. C., Rich A., Auron P. E. Transcriptional regulation of the human prointerleukin 1 beta gene. J Immunol. 1987 Jun 1;138(11):3972–3979. [PubMed] [Google Scholar]
  16. Furutani Y., Notake M., Fukui T., Ohue M., Nomura H., Yamada M., Nakamura S. Complete nucleotide sequence of the gene for human interleukin 1 alpha. Nucleic Acids Res. 1986 Apr 25;14(8):3167–3179. doi: 10.1093/nar/14.8.3167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Georgilis K., Schaefer C., Dinarello C. A., Klempner M. S. Human recombinant interleukin 1 beta has no effect on intracellular calcium or on functional responses of human neutrophils. J Immunol. 1987 May 15;138(10):3403–3407. [PubMed] [Google Scholar]
  18. Gery I., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. II. The cellular source of potentiating mediator(s). J Exp Med. 1972 Jul 1;136(1):143–155. doi: 10.1084/jem.136.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Krane S. M., Dayer J. M., Simon L. S., Byrne M. S. Mononuclear cell-conditioned medium containing mononuclear cell factor (MCF), homologous with interleukin 1, stimulates collagen and fibronectin synthesis by adherent rheumatoid synovial cells: effects of prostaglandin E2 and indomethacin. Coll Relat Res. 1985 Mar;5(2):99–117. doi: 10.1016/s0174-173x(85)80033-9. [DOI] [PubMed] [Google Scholar]
  20. Kurt-Jones E. A., Kiely J. M., Unanue E. R. Conditions required for expression of membrane IL 1 on B cells. J Immunol. 1985 Sep;135(3):1548–1550. [PubMed] [Google Scholar]
  21. Lepe-Zuniga J. L., Gery I. Production of intra- and extracellular interleukin-1 (IL-1) by human monocytes. Clin Immunol Immunopathol. 1984 May;31(2):222–230. doi: 10.1016/0090-1229(84)90242-3. [DOI] [PubMed] [Google Scholar]
  22. Libby P., Ordovas J. M., Birinyi L. K., Auger K. R., Dinarello C. A. Inducible interleukin-1 gene expression in human vascular smooth muscle cells. J Clin Invest. 1986 Dec;78(6):1432–1438. doi: 10.1172/JCI112732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lomedico P. T., Gubler U., Hellmann C. P., Dukovich M., Giri J. G., Pan Y. C., Collier K., Semionow R., Chua A. O., Mizel S. B. Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. 1984 Nov 29-Dec 5Nature. 312(5993):458–462. doi: 10.1038/312458a0. [DOI] [PubMed] [Google Scholar]
  24. Matsushima K., Taguchi M., Kovacs E. J., Young H. A., Oppenheim J. J. Intracellular localization of human monocyte associated interleukin 1 (IL 1) activity and release of biologically active IL 1 from monocytes by trypsin and plasmin. J Immunol. 1986 Apr 15;136(8):2883–2891. [PubMed] [Google Scholar]
  25. Matsushima K., Yodoi J., Tagaya Y., Oppenheim J. J. Down-regulation of interleukin 1 (IL 1) receptor expression by IL 1 and fate of internalized 125I-labeled IL 1 beta in a human large granular lymphocyte cell line. J Immunol. 1986 Nov 15;137(10):3183–3188. [PubMed] [Google Scholar]
  26. McCarthy D. O., Kluger M. J., Vander A. J. Suppression of food intake during infection: is interleukin-1 involved? Am J Clin Nutr. 1985 Dec;42(6):1179–1182. doi: 10.1093/ajcn/42.6.1179. [DOI] [PubMed] [Google Scholar]
  27. Merriman C. R., Pulliam L. A., Kampschmidt R. F. Comparison of leukocytic pyrogen and leukocytic endogenous mediator. Proc Soc Exp Biol Med. 1977 Feb;154(2):224–227. doi: 10.3181/00379727-154-39642. [DOI] [PubMed] [Google Scholar]
  28. Mizel S. B., Kilian P. L., Lewis J. C., Paganelli K. A., Chizzonite R. A. The interleukin 1 receptor. Dynamics of interleukin 1 binding and internalization in T cells and fibroblasts. J Immunol. 1987 May 1;138(9):2906–2912. [PubMed] [Google Scholar]
  29. Murphy P. A., Chesney P. J., Wood W. B., Jr Further purification of rabbit leukocyte pyrogen. J Lab Clin Med. 1974 Feb;83(2):310–322. [PubMed] [Google Scholar]
  30. Neta R., Douches S., Oppenheim J. J. Interleukin 1 is a radioprotector. J Immunol. 1986 Apr 1;136(7):2483–2485. [PubMed] [Google Scholar]
  31. Okusawa S., Gelfand J. A., Ikejima T., Connolly R. J., Dinarello C. A. Interleukin 1 induces a shock-like state in rabbits. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition. J Clin Invest. 1988 Apr;81(4):1162–1172. doi: 10.1172/JCI113431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Perlmutter D. H., Dinarello C. A., Punsal P. I., Colten H. R. Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. J Clin Invest. 1986 Nov;78(5):1349–1354. doi: 10.1172/JCI112721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ricci F., Stein E. M. Oscillatory singular integrals and harmonic analysis on nilpotent groups. Proc Natl Acad Sci U S A. 1986 Jan;83(1):1–3. doi: 10.1073/pnas.83.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stephan R. N., Saizawa M., Conrad P. J., Dean R. E., Geha A. S., Chaudry I. H. Depressed antigen presentation function and membrane interleukin-1 activity of peritoneal macrophages after laparotomy. Surgery. 1987 Aug;102(2):147–154. [PubMed] [Google Scholar]
  35. Van Damme J., Opdenakker G., Simpson R. J., Rubira M. R., Cayphas S., Vink A., Billiau A., Van Snick J. Identification of the human 26-kD protein, interferon beta 2 (IFN-beta 2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor. J Exp Med. 1987 Mar 1;165(3):914–919. doi: 10.1084/jem.165.3.914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Webb A. C., Collins K. L., Auron P. E., Eddy R. L., Nakai H., Byers M. G., Haley L. L., Henry W. M., Shows T. B. Interleukin-1 gene (IL1) assigned to long arm of human chromosome 2. Lymphokine Res. 1986 Spring;5(2):77–85. [PubMed] [Google Scholar]
  37. van der Meer J. W., Barza M., Wolff S. M., Dinarello C. A. A low dose of recombinant interleukin 1 protects granulocytopenic mice from lethal gram-negative infection. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1620–1623. doi: 10.1073/pnas.85.5.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]

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