The systemic administration of gamma interferon inhibits collagen synthesis and acute inflammation in a murine skin wounding model.
The ability of gamma interferon (IFN-gamma) 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-gamma (rMuIFN-gamma) (8.7 X 10(3) 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-gamma. 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-gamma 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-gamma also decreased the cutaneous accumulation of neutrophils induced by known proinflammatory mediators, such as interleukin 1 and activated serum. Thus, systemically administered IFN-gamma 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.
Granstein
R D
RD
Department of Dermatology, Massachusetts General Hospital, Boston 02114.
Deak
M R
MR
Jacques
S L
SL
Margolis
R J
RJ
Flotte
T J
TJ
Whitaker
D
D
Long
F H
FH
Amento
E P
EP
D000208:Acute Disease; D000818:Animals; D002056:Burns / Q000150:complications*; D003094:Collagen / Q000096:biosynthesis*; D003872:Dermatitis / Q000209:etiology / Q000378:metabolism*; D004890:Erythema / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006820:Hyaluronic Acid / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D007797:Laminin / Q000378:metabolism; D007834:Lasers; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins; D012867:Skin / Q000528:radiation effects / Q000648:ultrastructure; D012881:Skin Temperature / Q000187:drug effects; D014945:Wound Healing
D005353:Fibronectins; D007797:Laminin; D011994:Recombinant Proteins; D007371:Interferon-gamma; D006820:Hyaluronic Acid; D003094:Collagen