Biological basis for the clinical use of interferon F Dianzani

Interferons are proteins produced by certain cells in response to stimuli such as foreign cells (including tumour cells), bacteria, and viral antigens. They interact both with the interferon producing cells and other cells through production of effector proteins. There are three main types ofinterferons, known as (x, 1, and -y, which have direct antiviral and immunomodulatory effects. Antiviral effects may include inhibition of viral replication, protein synthesis, maturation, or release from infected cells. Immunomodulating effects may include enhancement of macrophage, cytotoxic T cell, and natural killer cell activity. In chronic viral hepatitis, the precise mechanisms of action of at interferon are not yet certain. Patients with chronic hepatitis B, however, have been shown to lack endogenous interferon production; those who respond to a interferon treatment show a characteristic peak in serum aminotransferase activity before resolution of the infection, indicating an immune reaction. In chronic hepatitis C, the antiviral effect may be more important; patients who respond to oa interferon tend to have higher values of 2'5' oligo adenylate synthetase, an enzyme induced by interferons that breaks down viral RNA. The clinical relevance of antiinterferon neutralising antibodies produced by some patients during interferon treatment has yet to be firmly established. (Gut 1993; supplement: S74-S76) Institute ofVirology, University La Sapienza, Rome, Italy F Dianzani Correspondence to: Dr F Dianzani, Institute of Virology, University La Sapienza, Rome, Italy. Interferons are proteins produced by certain cells in response to various stimuli, including foreign nucleic acids, foreign cells (including tumour cells), bacteria, and viral antigens. In particular, they represent the body's first line of defence against viral infection. Once interferon is released by the cell, it interacts with specific receptors, either on the same cell or on other cells, by inducing effector proteins. Only when these effector proteins have been produced may the cell become resistant to viral infection. The effect of interferon is increased by the transfer of these proteins to cells that have not experienced interferon inducers or interferon. 1 There are at least 20 genes coding for three main types of interferon (ot, 1, and -y), and at least another 23 genes coding for the effector proteins. Interferon, produced mainly by fibroblasts and epithelial cells, was the first to be discovered2 and is also the first to appear in response to viral infection. ot Interferon is produced by B lymphocytes, null lymphocytes, and macrophages,3 and differs both antigenically and structurally from 1 interferon. y Interferon differs molecularly and antigenically from both the other interferons and is produced by T lymphocytes sensitised to foreign antigens.