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. 1986 Mar;77(3):1020–1027. doi: 10.1172/JCI112354

In vivo inflammatory activity of epidermal cell-derived thymocyte activating factor and recombinant interleukin 1 in the mouse.

R D Granstein, R Margolis, S B Mizel, D N Sauder
PMCID: PMC423509  PMID: 3512598

Abstract

Epidermal cell-derived thymocyte activating factor (ETAF), a cytokine produced by keratinocytes, has previously been shown to be biochemically and functionally very similar, if not identical, to interleukin 1 (IL-1). Both ETAF and IL-1 have been demonstrated to be chemotactic for neutrophils and mononuclear cells in vitro. In order to demonstrate that this activity has physiological relevance we have used a simple in vivo model. The present study demonstrates that injection of high-titer ETAF or purified recombinant murine IL-1 into the mouse footpad results in an influx of neutrophils into the site with peak accumulation at 4 h. Footpad swelling also occurs with a time course roughly paralleling that of the neutrophil accumulation. Injection of control proteins failed to reproduce this phenomenon. Margination of neutrophils within blood vessels was seen within 1 h of injection of ETAF or IL-1, followed by entry into the stroma by 4 h. This suggests that chemotactic activity and not merely increased adherence or inhibition of migration is occurring. 5-10 d of daily, subcutaneous injection of ETAF on the mouse flank resulted in an infiltrate of neutrophils, and to a lesser degree, mononuclear cells in association with epidermal hyperplasia, subcutaneous fibrosis, and focal muscle necrosis in the panniculus carnosus. These findings were not seen in control sites injected with media. These findings provide direct in vivo experimental evidence suggesting a physiologic role for ETAF/IL-1 in local inflammation.

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Selected References

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

  1. Baracos V., Rodemann H. P., Dinarello C. A., Goldberg A. L. Stimulation of muscle protein degradation and prostaglandin E2 release by leukocytic pyrogen (interleukin-1). A mechanism for the increased degradation of muscle proteins during fever. N Engl J Med. 1983 Mar 10;308(10):553–558. doi: 10.1056/NEJM198303103081002. [DOI] [PubMed] [Google Scholar]
  2. Dempsey R. A., Dinarello C. A., Mier J. W., Rosenwasser L. J., Allegretta M., Brown T. E., Parkinson D. R. The differential effects of human leukocyte pyrogen/lymphocyte-activating factor, T cell growth factor, and interferon on human natural killer activity. J Immunol. 1982 Dec;129(6):2504–2510. [PubMed] [Google Scholar]
  3. Dinarello C. A. Interleukin-1 and the pathogenesis of the acute-phase response. N Engl J Med. 1984 Nov 29;311(22):1413–1418. doi: 10.1056/NEJM198411293112205. [DOI] [PubMed] [Google Scholar]
  4. Dinarello C. A., Wolff S. M. Molecular basis of fever in humans. Am J Med. 1982 May;72(5):799–819. doi: 10.1016/0002-9343(82)90548-4. [DOI] [PubMed] [Google Scholar]
  5. Falkoff R. J., Muraguchi A., Hong J. X., Butler J. L., Dinarello C. A., Fauci A. S. The effects of interleukin 1 on human B cell activation and proliferation. J Immunol. 1983 Aug;131(2):801–805. [PubMed] [Google Scholar]
  6. Gervais F., Stevenson M., Skamene E. Genetic control of resistance to Listeria monocytogenes: regulation of leukocyte inflammatory responses by the Hc locus. J Immunol. 1984 Apr;132(4):2078–2083. [PubMed] [Google Scholar]
  7. Kaye J., Gillis S., Mizel S. B., Shevach E. M., Malek T. R., Dinarello C. A., Lachman L. B., Janeway C. A., Jr Growth of a cloned helper T cell line induced by a monoclonal antibody specific for the antigen receptor: interleukin 1 is required for the expression of receptors for interleukin 2. J Immunol. 1984 Sep;133(3):1339–1345. [PubMed] [Google Scholar]
  8. Klempner M. S., Dinarello C. A., Gallin J. I. Human leukocytic pyrogen induces release of specific granule contents from human neutrophils. J Clin Invest. 1978 May;61(5):1330–1336. doi: 10.1172/JCI109050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Krueger J. M., Walter J., Dinarello C. A., Wolff S. M., Chedid L. Sleep-promoting effects of endogenous pyrogen (interleukin-1). Am J Physiol. 1984 Jun;246(6 Pt 2):R994–R999. doi: 10.1152/ajpregu.1984.246.6.R994. [DOI] [PubMed] [Google Scholar]
  10. Levin J., Tomasulo P. A., Oser R. S. Detection of endotoxin in human blood and demonstration of an inhibitor. J Lab Clin Med. 1970 Jun;75(6):903–911. [PubMed] [Google Scholar]
  11. Lipsky P. E., Thompson P. A., Rosenwasser L. J., Dinarello C. A. The role of interleukin 1 in human B cell activation: inhibition of B cell proliferation and the generation of immunoglobulin-secreting cells by an antibody against human leukocytic pyrogen. J Immunol. 1983 Jun;130(6):2708–2714. [PubMed] [Google Scholar]
  12. 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]
  13. Luger T. A., Charon J. A., Colot M., Micksche M., Oppenheim J. J. Chemotactic properties of partially purified human epidermal cell-derived thymocyte-activating factor (ETAF) for polymorphonuclear and mononuclear cells. J Immunol. 1983 Aug;131(2):816–820. [PubMed] [Google Scholar]
  14. Luger T. A., Stadler B. M., Katz S. I., Oppenheim J. J. Epidermal cell (keratinocyte)-derived thymocyte-activating factor (ETAF). J Immunol. 1981 Oct;127(4):1493–1498. [PubMed] [Google Scholar]
  15. Luger T. A., Stadler B. M., Luger B. M., Sztein M. B., Schmidt J. A., Hawley-Nelson P., Grabner G., Oppenheim J. J. Characteristics of an epidermal cell thymocyte-activating factor (ETAF) produced by human epidermal cells and a human squamous cell carcinoma cell line. J Invest Dermatol. 1983 Sep;81(3):187–193. doi: 10.1111/1523-1747.ep12517658. [DOI] [PubMed] [Google Scholar]
  16. Miossec P., Yu C. L., Ziff M. Lymphocyte chemotactic activity of human interleukin 1. J Immunol. 1984 Oct;133(4):2007–2011. [PubMed] [Google Scholar]
  17. Mizel S. B., Mizel D. Purification to apparent homogeneity of murine interleukin 1. J Immunol. 1981 Mar;126(3):834–837. [PubMed] [Google Scholar]
  18. Oppenheim J. J., Stadler B. M., Siraganian R. P., Mage M., Mathieson B. Lymphokines: their role in lymphocyte responses. Properties of interleukin 1. Fed Proc. 1982 Feb;41(2):257–262. [PubMed] [Google Scholar]
  19. Pepys M. B., Baltz M. L. Acute phase proteins with special reference to C-reactive protein and related proteins (pentaxins) and serum amyloid A protein. Adv Immunol. 1983;34:141–212. doi: 10.1016/s0065-2776(08)60379-x. [DOI] [PubMed] [Google Scholar]
  20. Postlethwaite A. E., Lachman L. B., Kang A. H. Induction of fibroblast proliferation by interleukin-1 derived from human monocytic leukemia cells. Arthritis Rheum. 1984 Sep;27(9):995–1001. doi: 10.1002/art.1780270905. [DOI] [PubMed] [Google Scholar]
  21. Sauder D. N., Carter C. S., Katz S. I., Oppenheim J. J. Epidermal cell production of thymocyte activating factor (ETAF). J Invest Dermatol. 1982 Jul;79(1):34–39. doi: 10.1111/1523-1747.ep12510569. [DOI] [PubMed] [Google Scholar]
  22. Sauder D. N., Dinarello C. A., Morhenn V. B. Langerhans cell production of interleukin-1. J Invest Dermatol. 1984 Jun;82(6):605–607. doi: 10.1111/1523-1747.ep12261439. [DOI] [PubMed] [Google Scholar]
  23. Sauder D. N. Epidermal cytokines: properties of epidermal cell thymocyte-activating factor (ETAF). Lymphokine Res. 1984 Summer;3(4):145–151. [PubMed] [Google Scholar]
  24. Sauder D. N., Mounessa N. L., Katz S. I., Dinarello C. A., Gallin J. I. Chemotactic cytokines: the role of leukocytic pyrogen and epidermal cell thymocyte-activating factor in neutrophil chemotaxis. J Immunol. 1984 Feb;132(2):828–832. [PubMed] [Google Scholar]
  25. Smith K. A., Lachman L. B., Oppenheim J. J., Favata M. F. The functional relationship of the interleukins. J Exp Med. 1980 Jun 1;151(6):1551–1556. doi: 10.1084/jem.151.6.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sztein M. B., Luger T. A., Oppenheim J. J. An epidermal cell-derived cytokine triggers the in vivo synthesis of serum amyloid A by hepatocytes. J Immunol. 1982 Jul;129(1):87–90. [PubMed] [Google Scholar]

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