In both of our discussions the past few weeks cigarette
smoking was shown to be therapeutic in patients with ulcerative colitis, one of
the two main categories of inflammatory bowel disease. The mechanism by which
cigarettes treat ulcerative colitis is widely unknown; which prompted me to
look for some more recent studies done on the topic. I found a study that
mimicked cigarette smoking in mouse models for ulcerative colitis. The study
set out to measure the levels of certain immune cells in order to pin down
which cells are most effected by cigarette smoke. They found that while the
levels of T, NK, and NKT cells did not change, iNKT cells increased. Invariant
NKT cells (iNKT) are a subset of natural killer t cells that recognize lipids
that contain the CD1d marker. Studies done on these cells have shown that they
have both protective and harmful effects, depending on the situation.
Because of
this duality of iNKT, the researchers followed up and tried to determine if the
raised levels proved to be therapeutic for the mice. They artificially raised
the levels of iNKT in the mouse models and found that there was reduction of
both Th1 and Th17 cytokines, which are both pro-inflammatory. These findings
showed that the increase of iNKT in ulcerative colitis is in fact protective.
I found this study to be very interesting. Since as we all probably know, cigarette smoking is a dangerous habit, I felt that it was important to find out the mechanism of the therapeutic effect of cigarette smoking in ulcerative colitis. Once the mechanism is found out it would be possible to develop treatments that cause the downstream effects of cigarette smoking, without the many negative effects of actually smoking. I see this study as a base for a whole new method in treatment of ulcerative colitis. If a medication or procedure is able to increase the levels of iNKT the patients could enjoy the therapeutic effects that were shown in this study. I think that the findings of this study need to be researched more, but still show a lot of promise in the continued development of new methods to treat ulcerative colitis.
I found this study to be very interesting. Since as we all probably know, cigarette smoking is a dangerous habit, I felt that it was important to find out the mechanism of the therapeutic effect of cigarette smoking in ulcerative colitis. Once the mechanism is found out it would be possible to develop treatments that cause the downstream effects of cigarette smoking, without the many negative effects of actually smoking. I see this study as a base for a whole new method in treatment of ulcerative colitis. If a medication or procedure is able to increase the levels of iNKT the patients could enjoy the therapeutic effects that were shown in this study. I think that the findings of this study need to be researched more, but still show a lot of promise in the continued development of new methods to treat ulcerative colitis.
Citations:
Montbarbon, Muriel, et al. "Colonic Inflammation in Mice Is Improved by Cigarette Smoke through iNKT Cells Recruitment." PloS one 8.4 (2013): e62208.
Hi, Joel. It is intriguing that the iNKT cells act as a sort of regulatory T cell to down-regulate cytokine production of Th1 and Th17 cells. Since the basis for giving people with Crohn’s disease worms is because it promotes Th2 cells to proliferate and in a way inhibit Th1, it would seem learning more about this mechanism could also be helpful in preventing or treating Crohn’s disease. It would be great if this mechanism could be studied further to see if it could help anyone with IBD in general.
ReplyDeleteMarissa, I completely agree. Since ulcerative colitis and crohns disease are normally so different, it would be great if there could be a treatment that is effective on both; especially if the treatment treats prevention of inflammation itself rather than just mitigating the downstream effects. The only problem I see with that is that ulcerative colitis primarily affects the colon, while crohns disease affects the entire digestive tract. Since the study focused on ulcerative colitis, they primarily measured the immune cell levels in the colon. It would be interesting is a different study measured levels in the entire digestive tract, which would be required for it to be an effective treatment for both crohns and ulcerative colitis.
ReplyDeleteFantastic post, Joel! I particularly enjoyed your discussion of iNKT downregulating proinflammatory cytokines produced by Th1 and Th17 cells. All this talk of downregulation makes me wonder: "What if these two processes are reciprocally regulated?" In other words, if the presence of iNKT inhibits production of inflammatory cytokines, is it possible that inflammatory cytokine presence might reduce iNKT production? If so, further studies in this area could lead to promising avenues of therapy.
ReplyDeleteJohn, thats an interesting thought. I think that a common thread connecting many biological processes is that the body can almost be seen as a complicated network of feedback loops trying to maintain homeostasis. In this way, I wouldn't be surprised if the inflammatory cytokines down regulate iNKT in a negative feedback loop of their own.
ReplyDeleteI found this discussion to be very interesting into the measured effects of inflammation markers of iNKT and the down regulation of Th1 and Th17. I am curious of what the exact mechanisms are as to get this effect in smokers, what of smoking changes this positive effect of smoking in those with ulcerative colitis. I find the concept of a trade off in helping minimize ulcerative colitis and the risk of lung disease form smoking to be very interesting. I would be interested to see if patients would actually make lifestyle change and begin smoking in order to prevent their ulcerative colitis symptoms. Would the risks that smoking presents be worth the tradeoff to patients for the benefit of ulcerative colitis management.
ReplyDeleteAmy, I totally agree. I think it is very important to study the mechanisms of how smoking helps patients with ulcerative colitis. That is why I think it was such a great result when the researchers found that smoking is correlated with an increase in iNKT cells. This is the first step in understanding more of the therapeutic "smoking pathway". I believe that we will be able to come up with increasingly better treatments as we keep adding details to that mechanism.
ReplyDeleteJoel, thank you so much for pointing out this mechanism, I naively mentioned in class how I believed stress reduction caused the therapeutic effects of smoking in patients with ulcerative colitis, and even though Dr. Cohen made a brief explanation of what actually took place, I was still intrigued by it. It would be interesting to see what specific funtion of iNKT leads to the therapeutic effects, perhaps it can be narrowed down and develop an exogenous treatment for individuals with the condition.
ReplyDelete