The systemic administration of gamma interferon inhibits collagen synthesis and acute inflammation in a murine skin wounding model

Richard D. Granstein, Mary Rose Deak, Steven L. Jacques, Randall J. Margolis, Thomas J. Flotte, Diana Whitaker, Frederick H. Long, Edward P. Amento

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

The ability of gamma interferon (IFN-γ) to affect cutaneous collagen synthesis in vivo was examined in a murine wounding model. Reproducible areas of full-thickness skin necrosis were produced by argon laser radiation. Mice received recombinant murine IFN-γ (rMuIFN-γ) (8.7 × 103 units/hr) over 14 d via osmotic pumps implanted subcutaneously or intraperitoneally. At 14 and 21 d after wounding, there was less fibrous tissue in healing scars of treated animals as determined by light and transmission electron microscopy. Associated with the decrease in connective tissue was an increase in the acid mucopolysaccharide content of healing scars, which was largely hyaluronate. Quantitative image analysis of electron micrographs confirmed that less collagen was present in healing scars of animals receiving rMuIFN-γ. The mean cross-sectional area of collagen fibers was smaller in specimens from treated mice, but no difference was seen in the size of collagen fibrils. The time required to obtain full skin closure was also delayed 23%-27% in treated animals. Using this injury model, we also found that rMuIFN-γ significantly reduced the degree of perilesional erythema surrounding the laser injury sites and, in the first 6 d after wounding, the degree of polymorphonuclear infiltrate present histologically at lesional sites. Indeed, rMuIFN-γ also decreased the cutaneous accumulation of neutrophils induced by known proinflammatory mediators, such as interleukin I and activated serum. Thus, systemically administered IFN-γ not only down-regulates collagen synthesis in the skin but also modulates in a previously unrecognized manner: neutrophil accumulation at sites of tissue injury in vivo.

Original languageEnglish (US)
Pages (from-to)18-27
Number of pages10
JournalJournal of Investigative Dermatology
Volume93
Issue number1
DOIs
StatePublished - Jul 1989
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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    Granstein, R. D., Deak, M. R., Jacques, S. L., Margolis, R. J., Flotte, T. J., Whitaker, D., Long, F. H., & Amento, E. P. (1989). The systemic administration of gamma interferon inhibits collagen synthesis and acute inflammation in a murine skin wounding model. Journal of Investigative Dermatology, 93(1), 18-27. https://doi.org/10.1111/1523-1747.ep12277336