Cytokines, particularly interferons (such as interferon-alpha), have a well-established scientific basis for use in the treatment of certain forms of hepatitis, especially chronic hepatitis B and C. Interferons are proteins that modulate the immune response and have antiviral activity. Clinical trials since the late 1980s and 1990s demonstrated that interferon therapy could reduce viral replication and improve liver function in patients with chronic viral hepatitis. For hepatitis C, combination therapy with interferon and ribavirin was the standard of care before the advent of direct-acting antivirals (DAAs).

The use of other cytokines in hepatitis is more experimental. Agents such as interleukin-12, interleukin-2, and others have been studied in preclinical or early clinical research, aiming to enhance immune-mediated clearance of hepatitis viruses. However, these are not mainstream therapies, and the bulk of clinical evidence and regulatory approval pertains to interferon-based regimens.

The evidence rating of 3 reflects robust support for interferons (a subclass of cytokines) but limited or investigational data for other cytokines. With the development of newer therapies, interferons are now less commonly used, especially for hepatitis C, but their historical role is well documented and scientifically validated.