Interferon: therapeutic fact or fiction for the '80s?

antigens and mixed lymphocyte reaction in severe pre-eclampsia. Br For many years it had been known that infection with one virus could protect animals against infection with another when, in 1957, Isaacs and Lindenmann1 discovered that medium from tissue cultures challenged with a killed virus could protect other cells against infection. The substances producing these effects are highly active glycoproteins known as interferons. They are released (in conjunction with many other unidentified molecules) from cells infected with virus or exposed to stimuli which mimic virus infection. Interferons probably act on cell membrane receptor sites causing intra-cellular production of proteins which mainly inhibit the translation of viral m-RNA. Interferons are relatively species-specific, having maximal activity in cells from the same or closely related species. Furthermore, there are three major types of human interferon with different molecular structures and different physico-chemical and antigenic properties. Preparations are arbitrarily defined by comparison with international standard preparations , and one unit of interferon is roughly the amount which reduces viral replication in tissue culture by half. Sources of interferon-Most clinical studies have been performed using human leucocyte interferon (HuIFNoa). This is made by exposing pooled buffy-coat lymphocytes to a para-influenza virus which may be inactivated later by acidification. The interferon thus obtained can be purified and concentrated by simple methods to 106-107 units per ml/mg protein for clinical use.2 The specific activity of pure human leucocyte interferon is about 109 U/mg protein, so clinical material is only about 041% pure. Most of the contaminating protein is probably albumin, but other proteins are present which may be biologically active. Interferon preparations have effects other than the inhibition of viral replication; for example, they inhibit cell growth and multiplication,3 enhance the expression of cell-surface antigens,4 suppress some functions of T and B lymphocytes,5 and enhance the activity of natural killer cells.6 7 Any of these functions may be responsible for the anti-neoplastic activity8 of interferons under current scrutiny. Preliminary clinical studies have also been performed with interferon derived from human fibroblasts induced with a synthetic double-stranded RNA (poly I:C). The yields are enhanced by the judicious use of metabolic inhibitors which suppress synthesis initially of cellular protein and then of RNA.9 Fibroblast interferon (HuIFNP) has also been purified to homogeneity (> 108 U/mg protein), but the clinical material has about the same activity as clinical leucocyte interferon. Fibroblast interferon is less stable than human leucocyte interferon, and …