Gamma-interferon inhibits collagen synthesis in vivo in the mouse.

Abstract

Subcutaneous implantation of osmotic pumps into CAF1 mice resulted in the formation of thick fibrous capsules around the pumps. When pumps were loaded with recombinant murine gamma-interferon (rMuIFN-'y) to deliver 2 X 103 U/h for 14 d, there was a marked decrease in thickness and collagen content of the capsules from rMuIFN-'y-treated animals compared with capsules from animals receiving diluent alone. The collagen content of the capsules was estimated by hydroxyproline analysis of the tissue and by quantitative electron microscopy of collagen bundles. Heat-inactivated rMuIFN-'y failed to reduce the fibrotic response in this assay. These results provide compelling evidence that gamma-interferon can down-regulate collagen synthesis in vivo and suggest the possibility that this lymphokine may be useful in the treatment of disease states characterized by excessive fibrosis.

Baculovirus-mediated interferon alleviates dimethylnitrosamine-induced liver cirrhosis symptoms in a murine model

“…[32][33][34][35] In vivo models of enhanced collagen synthesis have also revealed that IFN-g reduces the collagen accumulation associated with foreign bodies, skin wound healing and bleomycin-induced lung AcMNPV-mediated IFN alleviates LC in a murine model Y Nishibe et al fibrosis. [36][37][38] Further, in liver fibrosis induced by Schistosoma mansoni infection, IFN-g significantly reduces collagen accumulation, and type I and III procollagen mRNA levels. Hepatocyte growth factor (HGF) is one of a potent growth factors involved in liver regeneration and has a strong effect on epithelial and nonepithelial cells.…”

Animal experiment and clinical study of effect of gamma-interferon on hepatic fibrosis

“…Earlier report on the effect of IFN-γ anti-fibrosis could be found in 1984 [8] . Studies in vitro or in vivo later proved that IFN-γ had a better effect on hepatic fibrosis [9][10][11][12][13][14] .…”

“…Studies on interferon-gamma (IFN-γ) in vitro or in vivo are increasing [1][2][3][4][5][6][7] . Although the interferons were initially described for their antiviral properties, IFN-γ has also been found to have significant effects against hepatic fibrosis and to inhibit the synthesis of extracellular matrix [8][9][10][11][12][13][14] . However, there have been few studies on the relationship between different doses and effects of IFN-γ for hepatic fibrosis.…”

STAT4 activation in smokers and patients with chronic obstructive pulmonary disease

“…Macrophage inhibitory factor, released alongside IFN-c, may also enhance macrophage tissue residency leading to increased lung destruction. IFN-c inhibits collagen expression in fibroblasts [28] and decreases transforming growth factor-b 1 expression and collagen synthesis in mice [29,30]. The finding of increased IFN-c immunopositivity in the epithelium and submucosa of mild/moderate COPD patients invites speculation as to whether enhanced IFN-c expression may account for the lack of subepithelial basement membrane thickening in the bronchial biopsies in COPD, as compared to asthma [31].…”