Interferons and collagen production

Abstract

The immunoregulatory, antiviral, and antiproliferative agents known as the interferons have profound effects on collagen synthesis. Interferons α, β and γ suppress collagen synthesis by dermal fibroblasts. In addition, interferon γ (IFN-γ) inhibits the constitutively increased collagen synthesis characteristic of fibroblasts derived from lesions of patients with scleroderma. IFN-γ also inhibits collagen synthesis by myofibroblasts and synovial fibroblast-like cells. Inhibition of collagen synthesis by IFN-γ is associated with a coordinate inhibition of transcription for types I and III collagen. In addition, IFN-γ suppresses levels of procollagen mRNA and type II collagen synthesis in human articular chondrocytes. In vivo studies in mice have demonstrated that IFN-γ inhibits the collagen synthesis associated with the fibrotic response to an implanted foreign body, bleomycin-induced pulmonary fibrosis, and the healing response to cutaneous thermal burns. In the latter case, while collagen content of the wound scar was decreased, hyaluronic acid was increased in mice receiving IFN-γ compared to controls. This is in accord with in vitro studies showing that, while interferons γ and β decrease production of glycosaminoglycans, IFN-γ increases production of glycosaminoglycans. Of interest, acute inflammation at sites of thermal injury, or when elicited by proinflammatory agents in separate experiments, also was suppressed in mice treated with IFN-γ. The means by which IFN-γ inhibits collagen synthesis involves transcriptional regulation. There is a single report that interferon α can decrease the size of a keloid of recent onset in a human patient. Because the interferons can inhibit collagen synthesis in vivo, further studies may be warranted to evaluate the usefulness of these agents in the treatment of disease states characterized by abnormal fibrotic responses as well as their potential for altering the healing response associated with particular therapeutic interventions. © 1990.