IL28A (Interferon-lambda 2; IFN-lambda 2), IL-28B/IFN-lambda 3, and IL-29/IFN-lambda 1 are type III interferons which are distantly related to IL-10 family and type I IFN family cytokines. Mature human IL-28A is an approximately 22-25 kDa protein that shares 66% amino acid (aa) sequence identity with mouse and rat IL-28A and shows cross-species activity. It shares 96% and 70% aa sequence identity with human IL-28B and IL-29, respectively. Type III interferons are upregulated in response to viral infection, and they act predominantly on epithelial cells through a receptor complex that contains IL-10 R beta and IL-28 R alpha /IFN-gamma R1. Type III IFNs function as anti-viral molecules and induce the upregulation of MHC class I antigen. IL-28A promotes the Th1 polarization of dendritic cells in the airway (e.g. production of IL-12 p70 and IFN-gamma ) and inhibits Th2 and Th17 mediated inflammation. In the liver, however, the IL-28A induced Th1 cytokine response contributes to inflammation in T cell mediated hepatitis. IL-28A additionally exhibits anti-tumor activity, in part by enhancing IL-12 dependent anti-tumor CTL responses in vivo. In contrast, it is up-regulated in invasive bladder cancer where it promotes tumor cell migration.

IFN gamma, also known as IFNG, is a secreted protein that belongs to the type II interferon family. IFN gamma is produced predominantly by natural killer and natural killer T cells as part of the innate immune response, and by CD4 and CD8 cytotoxic T lymphocyte effector T cells once antigen-specific immunity develops. IFN gamma has antiviral, immunoregulatory, and anti-tumor properties. IFNG, in addition to having antiviral activity, has important immunoregulatory functions, it is a potent activator of macrophages and has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons. The IFNG monomer consists of a core of six α-helices and an extended unfolded sequence in the C-terminal region. IFN gamma is critical for innate and adaptive immunity against viral and intracellular bacterial infections and tumor control. Aberrant IFN gamma expression is associated with some autoinflammatory and autoimmune diseases. The importance of IFN gamma in the immune system stems in part from its ability to inhibit viral replication directly, and most importantly from its immunostimulatory and immunomodulatory effects. IFNG also promotes NK cell activity.