ATC Group: L03AB Interferons

Recombinant interferon alfa-2b is a sterile, stable, formulation of highly purified interferon alfa-2b produced by recombinant DNA techniques. Interferons exert their cellular activities by binding to specific membrane receptors on the cell surface. Recombinant interferon alfa-2b has exhibited antiproliferative effects in studies employing both animal and human cell culture systems as well as human tumour xenografts in animals. It has demonstrated significant immunomodulatory activity in vitro.

Interferon alfacon-1 is a recombinant hybrid protein based on the consensus amino acid sequence of naturally occurring human type-I interferon alphas. Interferon alfacon-1 does not act directly on the hepatitis C virus but binds to the interferon cell-surface receptor leading to the production of several interferon-stimulated gene products. Interferons induce pleiotropic biologic responses which include antiviral, antiproliferative, and immunomodulatory effects, regulation of cell surface major histocompatibility antigen (HLA class I and class II) expression and regulation of cytokine expression.

Interferon beta-1a exerts its biological effects by binding to specific receptors on the surface of human cells. This binding initiates a complex cascade of intracellular events that leads to the expression of numerous interferon-induced gene products and markers. Whether the mechanism of action of interferon beta-1a in MS is mediated by the same pathway as the biological effects described above is not known because the pathophysiology of MS is not well established.

Interferon beta-1b has been shown to possess both antiviral and immunoregulatory activity. The mechanisms by which interferon beta-1b exerts its actions in multiple sclerosis are not clearly understood. However, it is known that the biological response-modifying properties of interferon beta-1b are mediated through its interactions with specific cell receptors found on the surface of human cells.

It is presumed that interferon gamma-1b increases macrophage cytotoxicity by enhancing the respiratory burst via generation of toxic oxygen metabolites capable of mediating the killing of intracellular micro-organisms.

Peginterferon beta-1a is an interferon conjugated to a single, linear 20 kDa methoxy poly(ethyleneglycol) molecule at the alpha-amino group of the N-terminal amino acid residue. A definitive mechanism of action of peginterferon beta-1a in multiple sclerosis (MS) is not known. Peginterferon beta-1a binds to the type I interferon receptor on the surface of cells and elicits a cascade of intracellular events leading to the regulation of interferon-responsive gene expression.

Peginterferon alpha-2a is a pegylated interferon alfa-2a that possesses the in vitro antiviral and antiproliferative activities that are characteristic of interferon alfa-2a. Peginterferon alpha-2a is indicated for the treatment of hepatitis B and C.

Peginterferon alpha-2b is a covalent conjugate of recombinant interferon alfa-2b with monomethoxy polyethylene glycol. Although the exact antiviral mode of action of recombinant interferon alfa-2b is unknown, it appears to alter the host cell metabolism. This action inhibits viral replication or if replication occurs, the progeny virions are unable to leave the cell.

Ropeginterferon alfa-2b is a recombinant interferon alfa-2b conjugated with a two-arm mPEG at a degree of substitution of 1 mole of polymer/mole of protein. Interferon alfa belongs to the class of type I interferons which exhibit their cellular effects by binding to a transmembrane receptor termed interferon alfa receptor (IFNAR). Binding to IFNAR initiates a downstream signalling cascade through the activation of kinases, particularly Janus kinase 1 (JAK1) and tyrosine kinase 2 (TYK2) and signal transducer and activator of transcription (STAT) proteins. Interferon alfa was shown to have an inhibitory effect on the proliferation of hematopoietic and bone marrow fibroblast progenitor cells and antagonised the action of growth factors and other cytokines that have a role in the development of myelofibrosis. These actions may be involved in the therapeutic effects of interferon alfa in polycythaemia vera.