October Special - IFN gamma Protein

With the purchase of a 25 µg vial of IFN gamma protein, you will receive a second 25 µg vial of the same IFN gamma protein at no cost. Offer expires 10/31/2013. Not valid with other specials or offers. Limit one no cost vial per order, 5 no cost vials per customer during the period of the special. Note "October 2013 Special" on your order. Our current selection of IFN gamma proteins includes, bovine, canine, chicken, dolphin, equine, feline, human, mouse, ovine, rabbit, & swine. This offer is available world-wide.

IFN-γ : “macrophage-activating factor” is just the tip of the iceberg

The role of IFN-γ as a pro-inflammatory cytokine that protects against intracellular pathogens has been well understood for decades. Originally called “macrophage-activating factor”, IFN-γ also has critical roles in many other processes and cell types, including leukocyte migration, Th1 development, antibody production and class switching, and cell growth inhibition. While loss of IFN-γ signaling results in severe susceptibility to intracellular pathogens, some viral infections, and impaired tumor surveillance, IFN-γ has also been associated with immunopathology in lupus, multiple sclerosis, and diabetes.

IFN-γ is a highly pleiotropic cytokine, inducing the production of an array of molecules involved in inflammation. [3] Macrophage activation by IFN-γ entails many pathways, including up-regulation of Class I and Class II antigen processing and presentation and pathogen recognition pathways. IFN-γ activation also induces many direct anti-microbial effects, such as increased pinocytosis and phagocytosis, the NADPH oxidase system, NO priming, tryptophan depletion, lysosomal enzymes, and antiviral enzymes. However, the effects of IFN-γ stimulation extend beyond the macrophage. Induction of microbicidal molecules also occurs in neutrophils, and the upregulation of antigen presentation pathways occurs in many cells. Additionally, IFN-γ plays an important role in coordinating the immune response, affecting leukocyte trafficking, Th1 development, antibody production and isotype switching. Further, IFN-γ regulates genes involved with proliferation, cell cycle, and apoptosis. Together, these functions highlight the vast impact of IFN-γ in inflammation, immunity, and cancer beyond the macrophage.

Despite the widespread effects of IFN-γ, loss of IFN-γ or IFN-γR signaling in both mice and humans results in no developmental defects or impairments in development of a normal immune system. [3] What is severely impacted is the immune response to intracellular bacterial infections, as well as some viral infections. Further, IFN-γ is critical for tumor surveillance. While loss of IFN-γ increases susceptibility to intracellular pathogens and tumor progression, IFN-γ can also lead to unnecessary inflammation, and has been associated with autoimmune conditions, including systemic lupus erythematosus (SLE), multiple sclerosis, and insulin-dependent diabetes mellitus. 

Although interferons were identified during work in chicken eggs, most of the succeeding work has focused in mammals. [1] Evidence of an IFN system has been found in most vertebrates, but the limited sequence homology to mammalian IFNs has made identifying and comparing these genes difficult. However, putative orthologs of IFN-γ have been identified in many mammals, birds, and fish, as well as within the frog genome. [1, 4] Despite this wide distribution, IFN-γ has low cross-reactivity between species. [1] All together, the data suggest that the IFN system plays a key role in immunity throughout the vertebrate species.

         IFN-γ is a critical component of both innate and adaptive immunity within vertebrates. While it may be best known as a macrophage activating factor, it has many additional pro-inflammatory and anti-microbial functions. Loss of IFN-γ signaling leads to severe susceptibility to intracellular pathogens, but IFN-γ is also associated with immunopathology. Learning to walk the fine line between too much and too little IFN-γ will be a critical task in the efforts to tune the inflammatory rheostat.

References:

1. U. Schultz et al, Dev. Comp. Immunol. 28:499 (2004).

2. S.V. Kotenko et al, Nat. Immunol. 4:69 (2003).

3. K. Schroder et al, J. Leuk. Bio. 75:163 (2004).

4. R. Savan et al, Cytokine Growth Factor Rev. 20:115 (2009).