Test Catalog

Test ID: TNFA    
Tumor Necrosis Factor, Plasma

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluation of patients with suspected systemic infection, in particular infection caused by gram-negative bacteria


Evaluation of patients with suspected chronic inflammatory disorders, such as rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, or cancers.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 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)

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

< or =2.8 pg/mL

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Varfolomeev E, Vucic D. Intracellular regulation of TNF activity in health and disease. Cytokine. 2018;101:26-32 2. Atretkhany KN, Gogoleva VS, Drutskaya MS, Nedospasov SA. Distinct modes of TNF signaling through its two receptors in health and disease. J Leukoc Biol. 2020 107:893-905 3. Salomon BL, Leclerc M, Tosello J, Ronin E, Piaggio E, Cohen JL. Tumor necrosis factor alpha and regulatory T cells in oncoimmunology. Front Immunol. 2018;9:444 4. Ridgley LA, Anderson AE, Pratt AG. What are the dominant cytokines in early rheumatoid arthritis? Curr Opin Rheumatol. 2018;30:207-214

5. Friedrich M, Pohin M, Powrie F: Cytokine networks in the pathophysiology of inflammatory bowel disease. Immunity. 2019;50:992-1006

6. Wilson JG, Simpson LJ, Ferreira AM, et al: Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis. JCI Insight. 2020;5(17):e140289

7. Li Y, Yuan L, Yang J, et al:. Changes in serum cytokines may predict therapeutic efficacy of tofacitinib in rheumatoid arthritis. Mediators Inflamm. 2019 Oct24;2019:5617431 8. Salomon BL: Insights into the biology and therapeutic implications of TNF and regulatory T cells. Nat Rev Rheumatol. 2021;17:487-504 9. Willrich MAV, Murray DL, Snyder MR: Tumor necrosis factor inhibitors: clinical utility in autoimmune diseases. Trans Res 2015;165:270-282