| Among the diverse set of human interferons (IFNs) and
interferon-like cytokines, the type I interferons present a very
intriguing group of proteins that includes 13 IFN-alpha(α)
subtypes, IFN-Beta(β), IFN-epsilon(ε), IFN-Kappa(κ) and
IFN-omega(ω). Each of these proteins, although able to bind
to and signal through the same IFN-α receptor, exhibits
differences in its biologic potency including the induction of
an antiviral state, inhibition of apoptosis, or modulation of the
inflammatory response (1).
The existence of such redundancy
in the cytokine family has been suggested to confer an
evolutionary advantage as phylogenetic analyses indicate that
proteins involved in antiviral activity originated before those
involved in adaptive immunity (2). The early appearance and
apparent evolutionary conservation of the multiple type I
interferon allelic variants within different species signifies the
importance in retaining such diversity at the immunological
level (3,4). This article will describe the utilisation of IFN-α
and IFN-β in recent clinical trials, together with those that
are FDA-approved and currently used to treat a variety of
conditions.
Human interferons are some of the most widely studied
molecules and represent proteins that are secreted from cells in
response to a wide variety of stimuli. Originally isolated by Isaacs
and Lindemann in 1957 as a material that protected cells against
viral infection, IFN is now readily produced and prescribed as
therapeutic treatment for a variety of auto-immune diseases, as
well as viral infections (5). It is, in fact, one of the most popular
substances being utilised in FDA-mandated clinical trials at
present. However, among the large set of type I interferon variants
that are produced in humans and other mammals, IFN-α2
(Roferon A, Intron A and Peg-Intron) and IFN-β (Avonex and
Rebif) remain the major ones that have been tapped for their
therapeutic potential in the clinic.
IFN SUBTYPES
The IFN-α subtypes are expressed as a family of
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