Bortezomib Prunes Inflammatory T Cells: Hope for Inflammatory Diseases that Make the Young Old and Make the Old Want to Die

Inflammatory diseases such as arthritis, inflammatory bowel disease, multiple sclerosis, lupus, and many more, can strike at any time. Such diseases can create such suffering and disability that they make young people old very quickly, and can make old people wish they were dead.

A fairly new drug in the proteasome inhibitor class, Bortezomib, is used to treat a cancer of the bone marrow cells, multiple myeloma. But now, scientists have discovered a new use for Bortezomib: killing off active and proliferating T cells that cause so much damage in inflammatory diseases -- while leaving the resting T cells alone.

Those looking for a new treatment for a range of inflammatory diseases like arthritis, multiple sclerosis, inflammatory bowel disease, and lupus may need to look no further than a drug already available for treating cancer. In a research report published in the July 2010 print issue of the Journal of Leukocyte Biology (http://www.jleukbio.org), Japanese scientists use mice to show that bortezomib, currently used to treat cancers that affect white blood cells, induces cell death only in harmful (active and proliferating) T cells, leaving the rest unharmed. If the results prove true in humans, it offers hope that this drugs or others similar to it might be used to treat inflammatory diseases without the side effects of current drugs that affect all T cells equally.

"Unfortunately, there are a lot of people who are suffering from autoimmune and inflammatory disease," said Koichi Yanaba, M.D., Ph.D., a scientist from the Department of Dermatology at Nagasaki University Graduate School of Biomedical Sciences who was involved in the research. "We believe that this new-type remedy for autoimmune and inflammatory disease could successfully treat them in the near future."

To make this discovery, scientists used two groups of mice—the first treated with bortezomib and the second with saline. Researchers induced contact hypersensitivity reaction with oxazolone, a chemical allergen used for immunological experiments and found that bortezomib significantly inhibited the contact hypersensitivity responses. Results strongly suggest that bortezomib treatment enhanced T cell death by inhibiting NF-kappa B activation, which plays a key role in regulating the immune response to infection. This in turn led to the suppression of inflammatory responses in immune cells by reducing interferon-gamma production. _Eurekalert

Inflammation complicates many diseases of old age, including Alzheimer's, heart disease, lung and other respiratory diseases, digestive system diseases, and so on. Finding better and more specific treatments for blocking excessive inflammation while allowing normal immune function to continue, would extend life for many and reduce morbidity for many more.