Anticancer Drug Inhibits Inflammatory Response in Mouse Model

The drug bortezomib, which is already approved for treatment of multiple myeloma, has been shown in a mouse model to have a potent anti-inflammatory effect and may have potential as a treatment for diseases such as arthritis, multiple sclerosis, inflammatory bowel disease, and lupus.

Bortezomib is a proteasome inhibitor, and as such blocks the production of an enzyme complex that normally plays a role in many metabolic processes related to cell growth. By doing this, the drug slows cell growth and can cause the cells to die. Although bortezomib also affects healthy cells, it has a much greater effect on cancer cells, as they are growing much more rapidly. While multiple mechanisms are likely to be involved, proteasome inhibition may prevent degradation of proapoptotic factors, permitting activation of programmed cell death in cancer cells dependent upon suppression of proapoptotic pathways.

In the current study, investigators at Nagasaki University (Japan) assessed the effect of bortezomib treatment on contact hypersensitivity (CHS) in mice. CHS is a cutaneous, T cell-dependent, inflammatory reaction mediated mainly by antigen-specific effector T cells.

The investigators reported in the July 2010 issue of the Journal of Leukocyte Biology that bortezomib treatment clearly inhibited CHS responses. The bortezomib-treated mice showed significantly decreased numbers of CD4+ and CD8+ T cells in the challenged skin and draining lymph nodes. Cytoplasmic gamma-interferon (IFN-gamma) production by CD4+ and CD8+ T cells in the draining lymph nodes was decreased substantially by bortezomib treatment, and the drug enhanced T cell apoptosis by inhibiting NF-kappaB (nuclear factor of kappa light polypeptide gene enhancer in B-cells) activation during CHS responses.

Thus, bortezomib treatment likely induced T cell death, thereby suppressing CHS responses by reducing IFN-gamma production.

"Unfortunately, there are a lot of people who are suffering from autoimmune and inflammatory diseases,” said first author Dr. Koichi Yanaba, professor of dermatology at Nagasaki University. "We believe that this new-type remedy for autoimmune and inflammatory disease could successfully treat them in the near future.”

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Nagasaki University