Saturday, June 28, 2008

Tumor necrosis factor

This sounds like a good thing, right? Produced by cells of the immune system, this protein's name implies that it is a sort of cellular "ace-in-the-hole," inducing death in wayward cells and their mutant offspring before a cancerous tumor is formed.

When first discovered in 1975, tumor necrosis factor (TNF) was noted to induce death in malignant cells in laboratory studies. Unfortunately, it is most complex in its actions, proving toxic to healthy cells and actually promoting the growth of certain kinds of cancer. TNF in the wrong place at the wrong time causes unwanted inflammation. This little troublemaker is a destructive party crasher in the joints of persons with rheumatoid arthritis, It also has destructive, pro-inflammatory effects in Crohn's colitis, smoking-related lung disease, atherosclerosis, Alzheimer's disease, and doubtless much more of that which ails us. It contributes to the profound wasting of AIDS and induces fever and shock in the face of overwhelming bacterial infections.

TNF is a good thing if you happen to do battle with a saber-toothed tiger, accidentally drive a Folsom point into your leg, or fall off your bicycle and scrape your knee. TNF is known as an 'acute phase reactant'; as the body's own EMT, it is one of the first responders at the scene of injury or infection. Produced by activated white cells and the endothelial cells that line blood vessels, TNF attracts bacteria-killing white cells known as neutrophils, promotes the passage of these cells through the blood vessel lining into damaged tissues, alerts the liver to produce pro-inflammatory molecules such as c-reactive protein or CRP, suppresses appetite, and promotes fever.

If TNF and company are activated, however, by cigarette smoke, doughnuts, McDonald's french fries, or too much waisted fat, this same immune response sets off a world of trouble in our arteries. Likewise, auto-immune diseases such as lupus or rheumatoid arthritis cause TNF inflammatory responses in joint spaces and other body tissues.

Body balance or homeostasis depends on equilibrium between troubleshooters such as TNF and peacemakers such TNF inhibitors. Therapies directed against TNF have changed the long-term outlook for patients with rheumatoid arthritis. These new drugs include TNF antibodies such as Remicade and Humira, and proteins that fuse with TNF such as Embrel. Early suppression of the joint-destroying inflammation associated with RA can prevent skeletal deformities and pain, markedly improving a patient's quality of life. Unfortunately, blocking a bad actor such as TNF which also has essential immune functions is not without problems. For one thing, TNF has an active role in the body's response to mycobacterial infections. As a result, cases of active tuberculosis have been reported with the use of anti-TNF agents.


Mauigirl said...

Very interesting analysis of the complex effects of Tumor Necrosis Factor! Thanks for the info!

Wendy said...

Wow - that's a lot of info. My niece is taking Remicaid Rx for her crohn's. She does not respond to Imuran. The good news is - it's working. She is looking much better and is eating once again.
Let's keep our fingers crossed that she doesn't develop anything nasty as a consequence.

PSPam said...

Nice to see a doctor taking the time to blog. Always educational! I worked at St. Anthony's Central back in the mid 70's to late 80's.
I see that you have done articles on Fatty Liver and Hepatitis A. Would LOVE to see an article about Hepatitis C - the unrecognized epidemic in this country. No vaccine and 4-5 times more prevalent than HIV and most don't know they have it because the liver is an uncomplaining organ.

Keep up the good work and thank you for sharing your knowledge.


Get Tested for Hep C! Get Vaccinated for Hep A and B.

femail doc said...

Hi Pam: Thanks for visiting. Interesting web-sites you have. I agree hep C would be a good topic--I had a patient recently diagnosed with that not via abnormal liver tests but after a lab test for rheumatoid factor came back positive!