Autoimmune conditions often involve debilitating inflammation. There are at least 70 distinct types of pathologies in this class, which includes rheumatoid arthritis, Crohn's disease, and psoriasis.
Both steroids and non-steroidal anti-inflammatory drugs have been used to treat inflammation for decades, with varying degrees of success. A different approach is now available, thanks to the success of the biotechnology industry.
Our immune systems produce a large number of biomolecules called cytokines that control the inflammatory reaction. One of these is called tumor necrosis factor, or TNF. It comes in two varieties, labeled alpha and beta, and is believed to be a key regulator of the entire class of pro-inflammatory cytokines. TNF binds to specific cell receptors to accomplish its mission. Thus, any drug that blocks this binding has potential to treat inflammatory damage.
The biotech industry has given us two approaches to blocking TNF. One is the use of monoclonal antibodies (Mab). There are four currently on the market, all with names that end in the letters “mab”: infliximab, adalimumab, certolizumab, and golimumab. Monoclonal antibodies are proteins produced from genetically engineered cell cultures. They must be handled with great care to prevent misfolding, and must be administered by injection. Antibodies generally “tag” foreign proteins for destruction by the immune system. The anti-TNF monoclonal antibodies are intended to simply block TNF from attaching to its receptors.
A second approach is to tie up TNF with receptors that are not attached to a cell. Etanercept (brand name Enbrel) is a protein produced by a different type of generically engineered cell culture. I think the name sounds similar to “intercept” and the function is like an intercepted pass in football: the drug takes the TNF molecule away from the intended receiver.
TNF blockers (also called inhibitors or antagonists) are praised as life-changing drugs for some patients. But there is a dark side to their power. Inflammation is on the body's first line of defense against infection, so these drugs leave the patients vulnerable to tuberculosis and other serious diseases. And as the name implies, tumor necrosis factor also plays a role in killing cancer cells. Paradoxically, TNF blockers also cause or exacerbate some autoimmune conditions including lupus. This effect is not understood.
The FDA updated the label requirements for this class of drugs in August 2009 to include stronger warnings about cancer and infections. The potential risks and benefits, both very high, make for difficult decisions about using TNF inhibitors.
References:
Gatto B, “Biologics targeted at TNF: design, production and challenges”, Reumatismo 2006;58(2):94-103.
Balancing the risks and benefits:
https://www.empowher.com/news/herarticle/2009/12/15/what-would-you-risk-save-your-eyesight
FDA information about tumor necrosis factor blockers
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm174474.htm
Linda Fugate is a scientist and writer in Austin, Texas. She has a Ph.D. in Physics and an M.S. in Macromolecular Science and Engineering. Her background includes academic and industrial research in materials science. She currently writes song lyrics and health articles.