Many of the articles we have looked at so far concerning arthritis have discussed the role of the proinflammatory cytokines IL-1 and TNF-alpha. However, one study looked at IL-17, another proinflammatory cytokine that is expressed inthe synovium of patients with rheumatoid arthritis. The ultimate goal of the study was to identify the role of IL-17 in the effector phase of arthritis. Polyclonal anti-murine IL-17 anitbody postive serum was used to treat mice with collagen induced arthritis (CIA) after the first signs of arthrits. The control rgoup was given normal rabbit serum. Anti-IL-17 anitbody or control serum was also given to mice with later stages of CIA. The results showed that the severity of CIA was significantly reduced with anti-IL-17 antibody treatment. Joint damage was supressed in the knees and ankles of the mice, and inflammation was also supressed. More specifically, blocking of IL-17 also prevented focal bone erosion, and supressed serum IL-6 levels. A reduced number of cells expressing RANKL and IL-beta was also observed after anti-IL-17 treatment. Anti-IL-17 treatment was also effective in the later stages of CIA. The results showed that after a single injection with the anti-IL-17 antibody, the progression of the arthritis in the knee and ankle of the mice was significantly slowed. This shows that IL-17 does indeed play a role in the prolongation of arthritis. This study is important because it analyzes the role of IL-17 in arthritis as well as the relationship between IL-17 and other proinflammatory cytokines such as IL-1, TNF-alpha and IL-6, which is critical in the development of future therapies for arthritis. Overall, this study was well laid out and showed extremely promising results; however, one question that has bothered me when reading many of the articles this semester: have there been any observed side effects of these treatments? And if so, why does it seem as though adverse side effects are never discussed?
(1) Erik Lubberts, et all. Treatment with a neutralizing anti-murine interleukin-17 antibody after the onset of collagen-induced arthritis reduces joint inflammation, cartilage destruction, and bone erosion. Arthrits and Rheumatism. 50(2) 650-659. 2004
Subscribe to:
Post Comments (Atom)
3 comments:
Katie, did the article mention possible mechanisms?
Interesting question about the side effects. I am not sure why side effects are not tested or discussed. Most likely due to the fact that side effects are two words that no one likes to hear. When taking a certain drugs everyone wishes and hopes to believe that this drug will cure their problem without anymore complications. Unfortunately this is not how it always works. Our bodies are so complicated that it is hard to make one drug that will specifically target just one aspect of our bodies without effecting others. Although no one likes to hear of side effects, I am sure that they shoule always be tested and mention when doing these types of experiments.
Katie,
Interesting article. I've seen similar studies where they treated CIA with an antibody specific to a subunit of IL-23 (a subunit that is shared by IL-12). Interestingly, apparently IL-23 is necessary for sustaining the population of cells that produce IL-17 (Th17).
I believe IL-17 is a pro-inflammatory cytokine which drives IL-6 expression as well. Therefore, by ablating IL-17 in the joints of these mice, it can reduce inflammation led by downstream effects of IL-17. This of course is a simplification... but this whole Th17 business is VERY interesting...
Post a Comment