What is the Difference Between TNF Alpha and Beta

The main difference between TNF alpha and beta is that TNF alpha is cachectin, produced by activated macrophages, whereas TNF-beta is lymphotoxin, produced by activated lymphocytes. 

TNF alpha and beta are two proteins in the TNF family. TNF (tumor necrosis factor) is an adipokine and a cytokine. 

Key Areas Covered

1. What is TNF Alpha
– Definition, Features, Importance
2. What is TNF Beta
– Definition, Features, Importance
3. Similarities Between TNF Alpha and TNF Beta
– Outline of Common Features
4. Difference Between TNF Alpha and Beta
– Comparison of Key Differences

Key Terms 

TNF Alpha, TNF Beta, Tumor Necrosis Factor

What is TNF Alpha 

TNF alpha is a cytokine with a pleiotropic effect on various cell types. It serves as a major regulator of the inflammatory responses. It is involved in the pathogenesis of autoimmune and inflammatory diseases. Structure-wise, TNF alpha is a protein with 157 amino acids. Also, it is a homotrimer. Importantly, the activated macrophages, lymphocytes, and natural killer cells. It triggers a series of inflammatory molecules that can be cytokines and chemokines. Additionally, it is in a soluble and transmembrane form. Initially synthesized precursor form is the transmembrane TNF alpha. The released forms of TNF alpha from the membrane occur as the soluble form.

Figure 1: TNF Alpha

Furthermore, the biological activities of the TNF alpha are mediated by the type 1 and 2 receptors. Type 1 TNF receptors express in all human tissues, while type 2 TNF receptors only express in immune cells. The two main biological functions mediated by TNF alpha through these receptors are inflammation and cell death. Other than inflammation, TNF alpha mediates tissue regeneration, host defense, cell proliferation, cell survival, apoptosis, and necroptosis. 

What is TNF Beta

TNF beta is the other cytokine of the TNF protein family, playing a key role in the pathogenesis of joint diseases such as rheumatoid arthritis (RA). Activated lymphocytes, including T, B, and natural killer cells, secrete TNF beta. Another name for the TNF beta is lymphotoxin α (LT-α). Importantly, TNF alpha, the other type of TNF protein, shows 35% identity and 50% homology to TNF beta. Therefore, both TNF alpha and TNF beta use the same receptors. Also, they show similar biological activity, such as inflammation and apoptosis. Both bind to the TNF type 1 and type 2 receptors.

Figure 2: TNF Beta

Moreover, RA is a chronic, systemic inflammatory autoimmune disease. The key feature of the disease is inflammation of synovial joints. It is accompanied by progressive joint degeneration with impairment and pain. Inflammatory cytokines increase in RA, such as TNF alpha, interleukin 1, and interleukin 6. The inhibition of the target-specific cytokines, such as TNF alpha, gives promising results for RA.  

Similarities Between TNF Alpha and TNF Beta

• TNF alpha and beta are the two proteins in the TNF family.
• They are adipokines.
• They promote insulin resistance.
• Both bind to the same receptors. 

Difference Between TNF Alpha and Beta

Definition

TNF alpha refers to an inflammatory cytokine produced by macrophages/monocytes during acute inflammation and is responsible for a diverse range of signaling events within cells, leading to necrosis or apoptosis. At the same time, TNF beta refers to lymphotoxin-alpha produced predominantly by mitogen-stimulated T-lymphocytes and leukocytes.

AKA

TNF alpha is also known as cachectin, while TNF beta is also known as lymphotoxin.

Production

Activated macrophages produce TNF alpha, while activated lymphocytes produce TNF beta.

Function

TNF alpha is a major regulator of the inflammatory response, while TNF beta participates in tumor immunity.  

Conclusion

In brief, TNF alpha and beta are two proteins in the TNF family. They are adipokines, promoting insulin resistance. TNF alpha is also known as cachectin, and the activated macrophages produce it. In comparison, TNF beta is also known as lymphotoxin, and activated lymphocytes produce it. Therefore, their production is the main difference between TNF alpha and TNF beta. 

References:

1. Jang DI, Lee AH, Shin HY, Song HR, Park JH, Kang TB, Lee SR, Yang SH. The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics. Int J Mol Sci. 2021 Mar 8;22(5):2719. doi: 10.3390/ijms22052719. PMID: 33800290; PMCID: PMC7962638.
2. Buhrmann, C., Shayan, P., Aggarwal, B.B. et al.Evidence that TNF-β (lymphotoxin α) can activate the inflammatory environment in human chondrocytes. Arthritis Res Ther 15, R202 (2013). https://doi.org/10.1186/ar4393 

Image Courtesy:

1. “TNF-Mediated Death and Survival Pathways” By Masmudur M. Rahman, Grant McFadden – Own work (CC-BY 1.0) via Commons Wikimedia
2. “SMAD apoptosis” By Jerome Walker – Own Work (CC-BY 2.5) via Commons Wikimedia