Skip to main content
PMC home page
International Journal of Experimental Pathology logoLink to International Journal of Experimental Pathology
. 1993 Feb;74(1):79–85.

Inhibition of wound healing in mice by local interferon alpha/beta injection.

A J Stout 1, I Gresser 1, W D Thompson 1
PMCID: PMC2002231  PMID: 7682435

Abstract

Tumour vascular endothelium has been observed previously to be damaged by local injection of interferon alpha/beta, apparently before the onset of necrosis and regression of experimental tumours. In order to distinguish the effect of interferon alpha/beta on the vasculature from direct effects on tumour, the angiogenesis of wound healing was chosen for study. Injection of interferon alpha/beta subcutaneously adjacent to each wound at days 0 to 4 resulted in a markedly reduced rate of healing with poor edge reunion by day 3. Histologically, there was delay in the initiation of proliferation of not only capillary buds, but also fibroblasts and, to a lesser extent, epithelium across the incision. Nevertheless, no endothelial injury was seen at light or electron microscopic level. Healing subsequently resumed the normal pattern, though delayed, day 9 wounds resembling normal day 5 wounds. We conclude that interferon alpha/beta inhibits wound healing in mice by inhibition of proliferation of many cell types in addition to endothelium.

Full text

PDF
79

Images in this article

80Figure 1
on p.80
82Figure 2
on p.82
83Figure 3
on p.83
84Figure 4
on p.84

Selected References

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

  1. Bhartiya D., Sklarsh J. W., Maheshwari R. K. Enhanced wound healing in animal models by interferon and an interferon inducer. J Cell Physiol. 1992 Feb;150(2):312–319. doi: 10.1002/jcp.1041500214. [DOI] [PubMed] [Google Scholar]
  2. Boëthius J., Blomgren H., Collins V. P., Greitz T., Strander H. The effect of systemic human interferon-alpha administration to patients with glioblastoma multiforme. Acta Neurochir (Wien) 1983;68(3-4):239–251. doi: 10.1007/BF01401182. [DOI] [PubMed] [Google Scholar]
  3. Brouty-Boyé D., Zetter B. R. Inhibition of cell motility by interferon. Science. 1980 May 2;208(4443):516–518. doi: 10.1126/science.6154315. [DOI] [PubMed] [Google Scholar]
  4. Dvorak H. F., Gresser I. Microvascular injury in pathogenesis of interferon-induced necrosis of subcutaneous tumors in mice. J Natl Cancer Inst. 1989 Apr 5;81(7):497–502. doi: 10.1093/jnci/81.7.497. [DOI] [PubMed] [Google Scholar]
  5. Dvorak H. F. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N Engl J Med. 1986 Dec 25;315(26):1650–1659. doi: 10.1056/NEJM198612253152606. [DOI] [PubMed] [Google Scholar]
  6. Frayssinet C., Gresser I., Tovey M., Lindahl P. Letter: Inhibitory effect of potent interferon preparations on the regeneration of mouse liver after partial hepatectomy. Nature. 1973 Sep 21;245(5421):146–147. doi: 10.1038/245146b0. [DOI] [PubMed] [Google Scholar]
  7. Friesel R., Komoriya A., Maciag T. Inhibition of endothelial cell proliferation by gamma-interferon. J Cell Biol. 1987 Mar;104(3):689–696. doi: 10.1083/jcb.104.3.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gresser I. Antitumor effects of interferon. Acta Oncol. 1989;28(3):347–353. doi: 10.3109/02841868909111205. [DOI] [PubMed] [Google Scholar]
  9. Gresser I., De Maeyer-Guignard J., Tovey M. G., De Maeyer E. Electrophoretically pure mouse interferon exerts multiple biologic effects. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5308–5312. doi: 10.1073/pnas.76.10.5308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Maheshwari R. K., Srikantan V., Bhartiya D., Kleinman H. K., Grant D. S. Differential effects of interferon gamma and alpha on in vitro model of angiogenesis. J Cell Physiol. 1991 Jan;146(1):164–169. doi: 10.1002/jcp.1041460121. [DOI] [PubMed] [Google Scholar]
  11. Orchard P. J., Smith C. M., 3rd, Woods W. G., Day D. L., Dehner L. P., Shapiro R. Treatment of haemangioendotheliomas with alpha interferon. Lancet. 1989 Sep 2;2(8662):565–567. doi: 10.1016/s0140-6736(89)90694-6. [DOI] [PubMed] [Google Scholar]
  12. Ross R. The fibroblast and wound repair. Biol Rev Camb Philos Soc. 1968 Feb;43(1):51–96. doi: 10.1111/j.1469-185x.1968.tb01109.x. [DOI] [PubMed] [Google Scholar]
  13. Sidky Y. A., Borden E. C. Inhibition of angiogenesis by interferons: effects on tumor- and lymphocyte-induced vascular responses. Cancer Res. 1987 Oct 1;47(19):5155–5161. [PubMed] [Google Scholar]
  14. Strander H. Interferon treatment of human neoplasia. Adv Cancer Res. 1986;46:1–265. [PubMed] [Google Scholar]
  15. Thompson W. D., Harvey J. A., Kazmi M. A., Stout A. J. Fibrinolysis and angiogenesis in wound healing. J Pathol. 1991 Dec;165(4):311–318. doi: 10.1002/path.1711650406. [DOI] [PubMed] [Google Scholar]
  16. Tovey M. G., Begon-Lours J., Gresser I. A method for the large scale production of potent interferon preparations. Proc Soc Exp Biol Med. 1974 Jul;146(3):809–815. doi: 10.3181/00379727-146-38196. [DOI] [PubMed] [Google Scholar]
  17. Tsuruoka N., Sugiyama M., Tawaragi Y., Tsujimoto M., Nishihara T., Goto T., Sato N. Inhibition of in vitro angiogenesis by lymphotoxin and interferon-gamma. Biochem Biophys Res Commun. 1988 Aug 30;155(1):429–435. doi: 10.1016/s0006-291x(88)81104-5. [DOI] [PubMed] [Google Scholar]
  18. White C. W., Sondheimer H. M., Crouch E. C., Wilson H., Fan L. L. Treatment of pulmonary hemangiomatosis with recombinant interferon alfa-2a. N Engl J Med. 1989 May 4;320(18):1197–1200. doi: 10.1056/NEJM198905043201807. [DOI] [PubMed] [Google Scholar]
  19. White C. W., Wolf S. J., Korones D. N., Sondheimer H. M., Tosi M. F., Yu A. Treatment of childhood angiomatous diseases with recombinant interferon alfa-2a. J Pediatr. 1991 Jan;118(1):59–66. doi: 10.1016/s0022-3476(05)81844-x. [DOI] [PubMed] [Google Scholar]
  20. Yaar M., Karassik R. L., Schnipper L. E., Gilchrest B. A. Effects of alpha and beta interferons on cultured human keratinocytes. J Invest Dermatol. 1985 Jul;85(1):70–74. doi: 10.1111/1523-1747.ep12275353. [DOI] [PubMed] [Google Scholar]

Articles from International Journal of Experimental Pathology are provided here courtesy of Wiley

RESOURCES