Clinical Information

Tumor necrosis factor-alpha (TNF-alpha) is a highly pleiotropic cytokine involved in a spectrum of physiological processes that control inflammation, anti-tumor responses, and homeostasis.(1-3) The main sources of TNF-alpha are macrophages and T cells; however, many other cell types such as B cells, neutrophils, and endothelial cells have been described to produce TNF-alpha. It is expressed as a type II transmembrane protein (mbTNF-alpha) but can be cleaved to its soluble form (sTNF-alpha) with increased biological activity. Targets for TNF-alpha include 2 type I transmembrane receptors, TNF receptor I (TNFR-I or CD120a) and TNF receptor II (TNFR-II or CD120b). (2, 3) TFNR-I is expressed on every cell type except erythrocytes while TNFR-II is found only on endothelial and immune cells and can be activated by mbTNF-alpha.(1-3)

 

Following infection, TNF-alpha produced by macrophages enhances the proliferation of T cells after stimulation with interleukin-2 (IL-2).(1) In the absence of IL-2, TNF-alpha induces the proliferation and differentiation of B cells. Due to its antitumor property, TNF-alpha can cause cell death via a number mechanisms and is also capable of chemotactic attraction of neutrophils. Additionally, it is capable of stimulating macrophages to produce acid phosphatase and collagenase, and osteoblasts to produce prostaglandin E2 and collagenase. These chemical mediators have been known to lead to bone resorption.(1-3)

 

Due to the significant proinflammatory and immunoregulatory functions of TNF-alpha, and the wide distribution of TNFRs, the deregulation of TNF-alpha is associated with the development of several immunologic disorders and prediction of disease outcomes.(1-7) Indeed, elevated levels of TNF-alpha in serum or plasma levels have been able to predict severity in some infectious diseases such as sepsis in bacterial infections or poor outcomes in coronavirus 2019 infections.(6) In addition, TNF-alpha has been implicated in post-transplant reactions, pathological mechanisms in certain autoimmune diseases (eg, rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis), and cancers.(1-5,7) With the FDA approval of biologic and biosimilar therapies targeting TNF-alpha in patients with these diseases, it is likely that measurement of TNF-alpha levels may be useful in management of treatment response.(4-9)