Chemistry Reference
In-Depth Information
gastrointestinal (GI) tract. IBD is most prevalent in North America and Europe (1.4
and 2.2 million sufferers, respectively)
1
while other, previously low-incidence areas
have reported an increased occurrence in recent years.
2
Environmental factors, such
as diet and degree of sanitation, are believed to play a role in the development of
IBD.
3
There is also a large body of evidence suggesting a genetic predisposition to
IBD, with genes such as CARD15/NOD2, OCTN1 and 2, and DLG5 all linked to
the development of IBD.
4
The role of genetics has been comprehensively reviewed by
Henckaerts and colleagues.
3
Although the exact etiology of IBD remains unknown,
it is believed to be the result of a dysfunctional interaction between the gut micro-
biota and the mucosal immune system.
6
While many speculate both CD and UC
may be instigated by similar mechanisms, there are a number of differences between
the two conditions. UC occurs primarily in the colon, extending proximally from
the rectum.
7,8
It is characterized by continuous inflammation of the colon, super-
ficial mucosal inflammation, increased neutrophil presence in the lamina propria
and crypts, and the production of proinflammatory mediators such as interleukin
(IL)-12 and tumor necrosis factor (TNF)-α.
9,10
CD is characterized by the aggrega-
tion of macrophages which promotes the formation of noncaseating granulomas.
11
In contrast to UC, CD can occur in any region of the GI tract, but is most com-
mon in the terminal ileum.
7
CD lesions often present as patchy, typically transmural,
inflammation.12
12
In addition to UC and CD, other conditions including collagenous
colitis, lymphocytic colitis, and Behçet's syndrome are classified as IBD. Symptoms
of IBD include abdominal pain, GI bleeding, malnutrition, and bloody diarrhea
13
;
extraintestinal manifestations have also been reported, and can include disorders of
the liver, lungs, eyes, and joints.
14
The mortality rates are 1.4 percent and 1.0 percent
for CD and UC, respectively.
7
Common therapies for IBD, including 5-aminosalicy-
lates, antibiotics, steroids, and growth factors, have been comprehensively reviewed
by Kozuch and Hanauer.
11
Although the exact pathogenesis of IBD remains unknown, four mechanisms
have been proposed to initiate the disorder. The first theory suggests that micro-
bial pathogens (e.g., mitogen-activated proteins) are detected by the host immune
system, which initiates an inflammatory immune response.
12
The second theory
proposes that an imbalance between commensal and pathogenic bacteria in the
microbiota leads to a reduced ratio of protective: aggressive bacterial species, as
well as reducing the availability of short-chain fatty acids (SCFAs), the primary
energy source for colonic epithelial cells.
12
Defective host-immunoregulation is the
third possible mechanism in which the host immune system is unable to distin-
guish between harmful and commensal bacteria.
12
It is unclear what event would
act as a trigger in this scenario, as a defective immune system could be present from
birth, although the disease may not manifest until later in life. Environmental fac-
tors could trigger these events in a genetically susceptible host. This would elicit an
immune response against commensal bacteria and disrupt gut homeostasis. Finally,
host genetic defects leading to defective bacterial killing and mucosal barrier func-
tion have been proposed.
12
Increased permeability of the epithelial barrier facilitates
the transfer of harmful luminal antigens into the surrounding intestinal tissue, while
