Interferon biological activities

Blatt LM, Davis JM, Klein SB, Taylor MW (1996) The biologic activity and molecular characterization of a novel synthetic interferon-alpha species, consensus interferon. J Interferon Cytokine Res 16 489 99... 

Goeddel D.V., Yelverton E., Ullrich A, Heyneker H.L., Miozzari G., Holmes W., Seeburg P.J., Dull T., May L, Stebbing N., Crea R., Maeda S., McCandliss R, Sloma A, Tabor J.M., Gross M., Eamilletti P.C. Pestka S. (1980) Human leukocyte interferon produced by E. coli is biologically active. Nature, 287,411-416. 

No one interferon will display all of these biological activities. Effects are initiated by the binding of the interferon to its specific cell surface receptor present in the plasma membrane of sensitive cells. IFN-a and -P display significant amino acid sequence homology (30 per cent), bind to the same receptor, induce similar biological activities and are acid stable. For these reasons, IFN-a and IFN-P are sometimes collectively referred to as type I interferons, or acid-stable interferons. 

IFN-y is evolutionarily distinct from the other interferons it binds to a separate receptor and induces a different range of biological activities. It is thus often referred to as type II interferon. 

Owing to their biological activities most interferons are of actual or likely use in the treatment of many medical conditions, including ... 

Not all type I interferons induce exactly the same range of responses, and the antiviral to antiproliferative activity ratio differs from one type I interferon to another. As all bind the same receptor, the molecular basis by which variation in biological activities is achieved is poorly understood as yet. 

Most interferons have now been produced in a variety of expression systems, including E. coli, fungi, yeast and some mammalian cell lines, such as CHO cell lines and monkey kidney cell lines. Most interferons currently in medical use are recombinant human (rh) products produced in E. coli. E. coli s inability to carry out post-translational modifications is irrelevant in most instances, as the majority of human IFN-as, as well as IFN- 3, are not normally glycosylated. Whereas IFN-y is glycosylated, the E. coli-derived unglycosylated form displays a biological activity similiar to the native human protein. 

A third biological activity of IL-2 pertinent to immunostimulation is its ability to promote the growth of NK cells. It also promotes further differentiation of NK cells, forming lymphokine-activated killer (LAK) cells, which exhibit an enhanced ability to kill tumour cells or virally infected cells directly. NK cells express the P and y IL-2 receptor subunits only thus, their stimulation by IL-2 requires elevated concentrations of this cytokine. NK cells are also activated by a variety of additional cytokines, including all interferons and TNF. 

Huizinga, T. W. J., Van Der Schoot, C. E., Roos, D., Weening, R. S. (1991). Induction of neutrophil Fc-y receptor 1 expression can be used as a marker for biologic activity of recombinant interferon-yin vivo. Blood 77,2088-90. 

Vandenbroeck et al.7 used an ELISA to determine the recovery of immu-noreactive porcine interferon-gamma (IFN-y) from E. coli inclusion bodies. The ELISA used a polyclonal coating antibody with detection by a MAb. The inclusion bodies were solubilized in diluted 6 M guanidine/HCl and IFN subsequently refolded by its removal. The antiviral activity of the interferon was measured with a bioassay using the cytopathic effect (CPE) of vesicular stomatitis virus (VSV) on bovine kidney cells. The results of this study showed that the immu-noreactivity measured by ELISA matched the biological activity measured by bioassay. 

Pharmacology The biological activity of peginterferon alfa-2b is derived from its interferon alfa-2b moiety. Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface and initiate a complex sequence of intracellular events. 

Goeddel, D.V., E. Yelverton, A. Ullrich, et al.. Human leukocyte interferon produced by E. coli is biologically active. Natnre, 1980. 287 411-67. 

In earlier investigations, it had been recognized335,536 that interferon retains full biological activity after removal of sialic acid, or after removal of 50% of the total carbohydrate.532 However, its apparent hy-drophobicity, and affinity for poly(ribonucleotides), are conferred only when glycosylation is unimpaired.337... 

Fish EN, Banerjee K, Stebbing N. The role of three domains in the biological activity of human interferon-a. J Interferon Res 1989 9 97-114. 

Zavodny PJ, Petro ME, Chiang TR, Narnia SK, Leibowitz PJ. Alterations of the amino terminus of murine interferon gamma expression and biological activity. J Interferon Res 1988 8 483-494. 

In this communication we extend our earlier observations, which primarily dealt with the antiviral action of mouse fibroblast interferon, to its antigrowth activity and to antiviral and antigrowth activities of mouse T-cell interferon. We will show that inhibition by common gangiiosides Is restricted to both activities of fibroblast interferon alone. T-cell interferon, although its biological activities are analogous to those of fibroblast Interferon, neither binds to nor Is inhibited by these glycol ipids. Furthermore we demonstrate that mouse leukemia L—1210 cells that were selected for resistance to fibroblast interferon (6), respond equally well to T-cell Interferon as the parent cells which are responsive to both Interferons. 

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