Inhibition of fibroblast chemotaxis by recombinant human interferon γ and interferon α

Abstract Interferons have recently been recognized as potent mediators in inflammatory processes, exerting profound effects on fibroblasts. The influence of interferons γ and α on the chemotactic movement of fibroblasts toward various attractants was, therefore, investigated. Normal human adult and embryonal dermal fibroblasts, fibrosarcoma‐derived fibroblasts and SV40‐transformed fibroblasts were tested against conditioned medium from fibroblasts, the chemotactic peptide C‐140 of fibronectin, platelet‐derived growth factor, and leukotriene B 4 as attractants in the presence or absence of the interferons. Interferons γ and α inhibited chemotaxis in a dose‐dependent manner and at concentrations at least as low as 10 −2 ng/ml. Inhibition was noticeable when the cells were exposed to interferon for as short a period as 60 minutes, and the effect was not readily reversible. Inhibition occurred when the cells came from sparse or dense cultures, but when platelet‐derived growth factor was the attractant and the cells had been grown at low density there was no inhibition. It is concluded that this is a specific effect, not to be wholly explained by overall increase in membrane rigidity. Inhibition of fibroblast chemotaxis by interferons may be an important regulatory mechanism during wound healing or fibrosis and metastatic spread of tumor cells.