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TNF - Tumor Necrosis Factor

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TNF - Tumor Necrosis Factor

The Tumor Necrosis Factors (TNFs) consist of two subtypes:
- TNF - alpha (TNF-α) - also known as "cachectin"
- TNF-α has a major role in many Pro-Inflammatory and/or autoimmune diseases[1]. It is the site of action of multiple Biologic Agents, or Biological Response Modifier (BRM)- treatments that target TNF-α, including:
- Humira (adalimumab)
- Simponi (golimumab)
- Remicade (infliximab)
- Enbrel (etanercept)
- Cimzia (certolizumab)

- TNF - beta (TNF-β) - also known as "lymphotoxin"[1].
- TNF-β is highly similar to TNF-α in certain regions of the protein
- TNF-β is an immunosuppressor[2]

Biological Effects of TNF-α in Health and Disease

- TNF-α is a major regulator of the response of the immune system to infection and tissue damage. It is primarily secreted by monocytes and macrophages (types of immune system cells).
- TNF-α is very important to normal functioning of the immune system by activating factors that help remove and destroy infectious microorganisms and assist in healing of damaged tissues.
- TNF-α is produced by immune cells at the site of infection and/or inflammation.[1]
- TNF-α can cause changes in almost all types of cells
- TNF-α-induced changes are broadly acting
- TNF-α-induced effects can be multiplied at each step (small changes in TNF-α lead to large changes in downstream effects).
TNF-α Effects in the Normal Immune Response
- TNF-α induces pro-inflammatory factors including: Interleukin 1 (IL1), IL6 - Interleukin 6 , IL-8, NF-kB, ROS (Reactive Oxygen Species), and prostaglandins.
- TNF-α can self-activate.
- TNF-α induces factors that increase cell - adhesion (cell - stickiness).
- Induces Cachexia (wasting, or weight loss)
- Causes fever
- In certain cell types TNF-α can cause them to mature or divide, or induce cell death of certain types of cancer cells.
TNF-α Role in Certain Diseases
Overproduction of TNF-α is implicated in many Autoimmune Diseases, Aphthous Ulcers, Septic Shock, and Graft-Versus Host Disease (GVHD).

TNF-α is highly expressed in Crohn's Disease (CD)[2]. Expression of TNF-α correlates with the area of the intestine affected by Crohn's Disease and correlates with clinical severity of the symptoms.

TNF-α is implicated in Rheumatoid Arthritis (RA). Increased TNF-α is found in synovial fluid and joints of active RA. TNF-α correlates with joint inflammation and joint damage in RA.

References


1. Vilcek J and Lee TH. Tumor Necrosis Factor. New insights into the molecular mechanisms of its multiple actions. J. Biol. Chem. 1991; 266(12):7313-7316. http://www.jbc.org/content/266/12/7313.full.pdf

2. Rizzo A, Pallone F, Monteleone G, et al. Intestinal inflammation and colorectal cancer: A double-edged sword? World J Gastroenterol. 2011;17(26):3092-3100. http://www.ncbi.nlm.nih.gov/pmc/arti...JG-17-3092.pdf



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