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1. What is Interferon?
The cytokine family
Cytokines are an important group of proteins realizing intercellular communications
among cells of the same tissue (paracrine) or of different tissues (endocrine). Such
communications are essential for the correct synchronized reactions of the cells of
different tissues. In the literature different designations are used to denote these factors:
lymphokines, monokines, interleukins, and growth factors, which are now unified under
the common name cytokines. The main cytokines include interleukins 1 to 18 (IL-1 to IL-
18); interferons , , and (IFN , IFN , and IFN , respectively); tumor necrosis factorsα β γ α β γ α
and (TNF and TNF ); colony-stimulating factors — granulocyte, macrophage, andβ α β
granulocyte-macrophage (CSF-G, CSF-M, CSF-GM, respectively); basic and acid
fibroblast growth factors (aFGF and bFGF); and others.
There are two types of human interferons, type I and type II, and interferon-like cytokines.
Type I human interferons consist of six classes: IFN- , IFN- , IFN- , IFN- , IFN- , andα β ε κ ω
IFN- . However, a largeν number of type I interferons are found in other animal species.
Type II interferon consists only of IFN- . In addition, three related human interferon-likeγ
cytokines have been reported: IL-28A, IL-28B, and IL-29. There is only one IFN- , IFN- ,β ε
IFN- , IFN- , and IFN- , but the IFN- proteinsκ ω ν α consist of twelve individual proteins.
Differences between IFN and IFN /γ α β
The main differences between IFN (type II) and IFN / (type I) are summarized asγ α β
follows:
 Different primary structure.
 The IFN / genes are not split, whereas the IFN gene has introns.α β γ
 IFN / share a common receptor that is different from that of IFN .α β γ
 The two types of interferons induce or suppress the synthesis ofdifferent proteins.
 IFN / stimulate mainly the activity of the natural killer (NK) cells,whereas IFNα β γ
stimulates mainly the macrophages.
 IFN / are stable at pH 2.0; IFN is acid labile.α β γ
 Differences are in the signaling pathway leading to the correspondingactivity.
The different receptors and the differences in the metabolic signaling pathways open
avenues for a combined clinical use of IFN and IFN or IFN and IFN . In the latterγ β γ α
case, the possible effect of IFN on the IFN receptor hasγ α to be taken into consideration.
This effect seems to depend on the cellular type. In the neuroblastoma cell line T98G,
IFN suppresses the binding ofγ IFN to its receptor, possibly by affecting its dissociationα

2. constant (Kd). In other tumor cell lines (melanoma HMV-1, kidney carcinoma ACHN,
Daudi lymphoma), IFN induces the receptors of IFNγ α but only under the condition that
IFN preceded the treatment with IFN .γ α
The Principal Properties of Interferon
Interferon possesses certain characteristic properties which distinguish it from other virus
inhibitors. These include:
1. Tissue and species specificity.
2. Insensitivity to the action of virus-neutralizing antibodies.
3. Resistance to the action of an acid medium and thermostability at 56 °C.
4. Sensitivity to proteolytic enzymes.
5. Ability to inhibit reproduction of certain viruses in tissuecultures, i.e., absence of
virus specificity.
Besides these properties, interferon also possesses others which characterize it as a
protein of low molecular weight with particular physicochemical properties. Details of the
various properties of interferon are given below.
Physicochemical Properties
Interferon is a protein of low molecular weight. Its molecule contains the following
components: tyrosine 2.3%, tryptophan 2.6%, arginine 7.2%, lysine 11.1%. It does not
contain nucleic acids and only traces of carbohydrate are present. Interferon has a
slightly acid reaction and contains disulfide bridges. The number of polypeptide chains
has not been established. However, the reaction of this protein is alkaline and the
isoelectric point is close to pH 6.9-7.1 or 7.2-7.8.
Species Specificity
One of the most important properties of interferon is its well-marked species specificity.
This property of interferon was first described by Tyrrell. In his experiments the
inhibitors obtained in the chorioallantoic membranes of the chick embryo and in cultures
of calf kidney cells possessed antiviral activity only in homologous cells. Isaacs and
Westwood also showed that vaccinal lesions in the rabbit’s skin were actively inhibited by
interferon produced in cultures of rabbit cells, whereas chick interferon gave a very weak
effect in such cases. The opposite effect was obtained in experiments on chick embryos,
i.e., only chick and not rabbit interferon was active. Later the marked species specificity
of interferon was confirmed by most investigations.
Antigenic Properties

3. The weakness of the antigenic properties of interferon is confirmed by the results
obtained by Falcoff and co-workers, who found that repeated intravenous injections of
human leukocytic interferon into adults and children were not accompanied by
the formation of any detectable quantities of antibodies. No antibodies could be detected
even in a child aged 6 years who received 3620 ml of leukocytic interferon intravenously
over a period of 400 days.
References:
Solov’ev, V. (2012). Interferon: Theory and Applications. Springer Science & Business
Media.
Tsanev, R. G., & Ivanov, I. (2001). Immune interferon: properties and clinical
applications. CRC Press.
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