Interleukin's Anti-inflammatory Effects Prolonged in Duke Study

Researchers at Duke University published a study whose results suggest that the team has devised a new way to significantly prolong the effects of the anti-inflammatory drug, interleukin-1, thus making it useful for providing longer-lasting treatment for osteoarthritis. The study can be found in the October 2006 issue of online magazine Journal of Controlled Release, and the team was lead by Lori Setton, associate professor of biomedical engineering and surgery.

In their study, the researchers modified interleukin-1 receptor antagonist (IL1RA), based on previous research that found that IL-1 heightens the activity of enzymes that damage joints by breaking down their bundles of collagen. The team found that the drug, which is a protein, could be improved by attaching a second protein that clumps together at normal body temperatures. This second protein attached belongs to the class of elastin-like polypeptides (ELPs). These types of protein aren't recognized by the body's immune system as foreign substances, and thus they have some unique advantages for biomedical applications. Also, ELPs can be joined directly to genes that control the production of various proteins in cells, with the combination forming "fusion proteins." As the proteins degrade, they yield simple amino acids, which are the building blocks of all proteins. The combined drug likewise would assemble into clumps in the body to serve as "drug depots" that gradually release active drug particles.

When injected into the knees of rats, the fusion protein proved to have a 25-fold longer half-life in the joint than a similar soluble protein. Half-life is the time required for half the quantity of the protein to be broken down and eliminated from the joint space. With this advance, the team believes treatments of osteoarthritis could go from twice a week to perhaps twice a month, constituting a huge clinical gain.

Further studies, however, suggested the fusion protein might do better in an arthritic joint. The researchers were surprised to find that the same inflammatory enzymes that destroy joint collagen also chew ELP from the original drug protein, thereby restoring its activity. With these results, the researchers plan to work with collaborators to test the modified drug's ability to interfere with the progression of disease in the joints of animals.

Article References
Prolonged Arthritis Relief Anticipated From New Engineered Drug, site accessed on 10/24/2006.