The Role of TNF in Inflammation Is both Pathogenic and Protective

A recent publication disclosed new information concerning the effects of delayed and chronic responses to tumor necrotic factor (TNF) signaling on the behavior of immune system macrophages. While much has been learned about early signaling pathways activated by TNF, little is known about delayed and chronic responses to TNF signaling.
Investigators at the Hospital for Special Surgery (New York, NY, USA) worked with both human blood cells and mice. As part of the study, they evaluated macrophage behavior during a two-day period after being stimulated with TNF.

They reported in the March 16, 2008, issue of the journal Nature Immunology that TNF initiated an interferon-beta-mediated autocrine loop that sustained expression of inflammatory genes and induced delayed expression of interferon-response genes such as those encoding the transcription factors STAT1 and IRF7, which enhance macrophage responses to stimulation of cytokines and Toll-like receptors.

"What we have described is that TNF has both pathogenic affects—it helps to sustain some of these inflammatory chemokines, but it also has a potential protective effect because some of these interferon responses limit the amount of cell proliferation and they can also help to limit inflammation,” explained senior author Dr. Lionel Ivashkiv, director of basic research at Hospital for Special Surgery. "The striking thing about many of these genes that came to our attention first was that there were these classic interferon response genes which had previously not been associated with TNF. It suggests a new mechanism by which TNF can drive and sustain inflammation.”


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