Interferon alpha (IFN alpha) showed multiple effects on melanoma. Firstly, IFN alpha has the potential of promoting antigen presentation and re-polarizing the immune response toward Th1 response. Secondly, IFN alpha helps the recruitment of T cells and NK to tumor tissue and promotes the survival of memory T cells. Thirdly, IFN alpha could inhibit the angiogenesis of melanoma. Finally, IFN alpha might directly inhibit the proliferation of melanoma cells.
The effect of IFN-α on DFS (disease-free survival) and OS (overall survival) in patients with high-risk cutaneous melanoma have been examined, the conclusion was IFN-α adjuvant treatment showed statistically significant improvement in both DFS and OS.
Interferons are not only the first line of defence against viral infections such as hepatitis C virus infections, but they also have important roles during the chronic phase of viral infections. For over 20 years now, recombinant interferon alpha has been used for the treatment of chronic hepatitis C. The molecular mechanisms responsible for non-response to interferon are still not completely understood, but systematic analysis of liver biopsies revealed that the spontaneous activation of the endogenous interferon system in the liver of patients with chronic hepatitis C prevented response to interferon-based therapies. Moreover, recent genomewide association studies found a highly significant and strong association between genetic variants near the IFNλ3 gene, designated the IL28B genotype, with spontaneous clearance of hepatitis C virus as well as with response to treatment of chronic hepatitis C with pegylated interferon alpha and ribavirin.
Interferon was the main therapy for chronic hepatitis C infection for years, but only 20% of patients showed sustained virological response. The efficacy was doubled by adding ribavirin to interferon. Pegylated interferon has recently been developed to further improve response rates. Its advantage is a prolonged half-life by covalent bonding of polyethylene glycol to interferon. Randomized trials have found that pegylated interferon increased the number of patients with sustained virological response, without increasing the risk of adverse events. Pegylated interferon plus ribavirin was superior to pegylated interferon monotherapy, and is considered the standard treatment for chronic hepatitis C.
When used in the systemic therapy, an intramuscular injection of interferons are mostly administered.Interferon injections in the vein, in the muscle, or under skin is generally well tolerated. The most common adverse effects of interferon injections are flu-like symptoms: feeling ill, fatigue, increased body temperature, headache, convulsion, dizziness, muscle pain, hair thinning, and depression. Erythema, pain and hardness on the spot of injection are also frequently observed. Interferon therapy causes immunosuppression, in particular through neutropenia and can result in some infections manifesting in unusual ways.
As with many other signaling proteins, interferons bring together two copies of a receptor to initiate the signal inside the cells. Interferons are relatively small proteins. Interferon-gamma is a dimeric protein, and it is composed of two identical chains, which intertwine extensively. Two copies of its receptor bind on either side of IFN-gamma. Interferon-alpha, on the other hand, is monomeric, composed of one chain, and two different receptor chains bind to different portions of the protein.
Alpha-interferons can modify immune function and gamma-interferon plays a role in defense. Apart from these duties in controlling abnormal growth, they also play supporting roles in the day-to-day maintenance of normal cellular growth levels. The messages are subtle and have different consequences when combined with the many messages passing from cell to cell. This complicates the use of interferon in therapy. Familiar hormones like insulin have simple, direct actions, so insulin is effective in replacement therapy. The artificial messages sent by interferon treatment, however, can be read incorrectly, leading to unwanted side effects. But in special cases, interferon can send just the right instructions, directing the immune system to destroy hairy cell leukemia cells or inhibiting the growth of blood vessels nourishing a Kaposi's sarcoma.