There's lots of cytokines involved (or show up in various research) because of their many roles - Cytokines generally speaking can be thought of as soluble molecules that bind to their respective cellular receptors. The difference found in most cases between Crohn's and Ulcerative Colitis is generally the adaptive vs. innate response respectively.
The commonality arises from the fact that TNFa is part of the TNF-TNF receptor family. TNFa can function either as a pro-inflammatory cytokine in some cases, yet in others it can actually trigger cell death (apoptosis). In our case with IBD, both TNFa and Histamine together stimulate the breakdown of tight junctions between epithelial cells - this is what causes the characteristic swelling of acute inflammation in our affected areas or throughout our colon in some people's cases like mine and NCOT's or Levi's with Crohn's-Colitis.
TNFa can do a lot of things as well - if TNFa is produced in large enough amounts it can signal to the bone marrow to increase the output of neutrophils (@AguywithUC) - which are found in very high levels in IBD and I believe (but am not 100% sure) but more so in Ulcerative Coltis than in Crohn's. Which also goes back to the difference between the two innate and adaptive immune responses between the two conditions:
TNFa is largely dependent on the NF-kB pathway, which I think we've all read about
or heard the term from time to time on here. Opposite to the above, when at low concentrations TNFa acts locally (or in the immediate area) to increase the expression of adhesion molecules on leukocytes AND to stimulate other cells to produce pro inflammatory molecules. When at high concentration as mentioned above, it actually stimulates epithelial cells to synthesize nitric oxide - hence the increase seen in IBD.
Now - what I find of utmost curiosity is that one of the main agents that induce TNF secretion is LPS (Lipopolysaccharides) from gram negative bacteria. - But I'm a bacteria guy.. and don't by into the auto-immune thing.
Interestingly as well - this is why before we take a drug such as Remicde we are tested for tuberculosis, because when this pathway is blocked it can lead to the re-emergence of active tuberculosis.
So in a nutshell we take Remicade more so as a means to reduce damage to our epithelial cells or the "swelling" so to speak and restore the tight junctions. This is why we have colonoscopies - to verify that these tight junctions have been restored and if so we are deemed in clinical remission. Though far from a cure lol.. But hey, we can get our lives back for a bit at least or well, at least for a period of time when it works, which it does not in some cases.
Inflammasomes, such as IFNy (Interferon Gamma) are pretty darn complicated (more so because no one knows a whole heck of a lot about
them). They can be activated by cell damage, by say sensing abnormal levels of potassium present inside our cells, as well as Reactive Oxygen Species. In our case IFNy is generally assumed to be involved in macrophage activation. Hence the Type 2 Inflammasome.
So generally it's the activation of macrophages and other immune cells that is very characteristic of IBD, hence why TNFa is mentioned often in research for both diseases (UC and Crohns), same with neutrophils and IFNy and NF-kB etc etc.
These can be either interpreted as an immune "disfunction" where our body is attacking something "self"... or our bodies ARE actually attacking something... and herein lies the whole mystery of IBD.
The flip side to this is that some bacteria can hide out in our macrophages where they replicate - more so, once inside or engulfed or eaten lol, they induce the expression of TNFa as a food source really is the easiest way to explain it. So they use TNFa for their reproductive benefit.
In any case, the above is why TNFa is common to both. Also, quickly in regards to the 50+ times more thing - This is more so that cells are already primed or "tuned" depending on how they are sampled like say for example they were sampled directly form the patients... leading more suspicion to bacterial nature of IBD versus autoimmune. There's a term for this "tuning" that escapes me at the moment, but I'll pop into my head tonight at some point lol. At has to do partly with Inflammasomes actually. Its sort of an "on high alert
" for inter-cellular bacteria.
Post Edited (Canada Mark) : 1/24/2014 3:45:01 PM (GMT-7)