Download The role of IL-12/IL-23 in Crohn`s disease

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The role of IL-12/IL-23 in Crohn’s disease
What is Crohn’s disease?
Crohn’s disease is a chronic inflammatory condition affecting the gastrointestinal (GI)
tract, most often occurring in the end of the small intestine (ileum) or the beginning of the
large intestine (colon), but may involve any part from the mouth to the anus. 1,2 In Europe
250,000 people are living with Crohn’s disease, with around 18,000 new cases diagnosed
each year.3 Though anyone can be affected by Crohn’s disease at any age, it most often
impacts those between the ages of 15 to 35 in both men and women.3
Crohn’s disease belongs to a group of conditions known as Inflammatory Bowel Diseases
(IBD) and is marked by an abnormal response from the body’s immune system to food,
bacteria and other materials in the intestine that are mistaken for foreign substances. 2
How is the immune system involved in Crohn’s disease?
The intestines are home to a complex mucosal immune system which is thought to interact
with bacteria (microbiota) that live in the gut in order to maintain homeostatic balance. If
the balance of the intestinal immune system is disrupted, it can make the normally
harmonious bacteria in the gut induce a response from the body’s own immune system. 4,5
The immune system’s initial first line response, known as the innate immune system, will
be activated; however, these short-term inflammatory processes may not be enough to
deal with the invasion and the adaptive immune response will then become activated. This
may result in acute intestinal inflammation which can usually be resolved by the
suppression of these pro-inflammatory immune responses and anti-inflammatory
mechanisms.6 However, in Crohn’s disease, the inflammation caused by the immune
response may not be resolved by these means and can, in turn, induce an uncontrolled
activation of the mucosal immune system leading to chronic intestinal inflammation. This
inflammation can cause further complications such as tissue destruction and ongoing
disease activity.6
What are IL-12 and IL-23 and how are they involved in Crohn’s disease?
Specific immune cells that form part of the immune response respond to certain bacteria
from the gut by producing signaling molecules known as cytokines that can promote
chronic inflammation of the GI tract and cause the symptoms of Crohn’s disease. 6 These
signalling molecules, among others, include interleukins (IL) -6, -10, -12, -23 and tumour
necrosis factor.6
IL-12 and IL-23 are small proteins that regulate the adaptive immune response and are
seen at increased levels in active Crohn’s disease.7 They are involved in the mucosal
immune response that responds to inflammation and the further activation and
recruitment of immune cells that contribute to uncontrolled chronic intestinal
inflammation.6,8,9
Why are IL-12 and IL-23 inhibitors potential treatments for Crohn’s disease?
IL-12 and IL-23 have been shown to have a fundamental role in controlling mucosal
inflammation and have therefore been identified as a relevant and realistic therapeutic
approach to target autoimmune driven diseases.10 Moreover, both IL-12 and IL-23 share
a common component known as the p40 subunit. There is evidence to show that therapies
which target the p40 subunit and inhibit parts of the inflammatory cascade, an approach
that has proved successful for psoriasis and psoriatic arthritis, are also credible therapeutic
agents for Crohn’s disease and are currently being assessed in clinical trials.10,11,12
March 2016
PHEM/IMM/0216/0003
For medical media only
References
1
www.ccfa.org/what-are-crohns-and-colitis/what-is-crohns-disease/.
http://www.cdc.gov/ibd/what-is-ibd.htm.
3
http://www.efpia.eu/diseases/78/59/Inflammatory-Bowel-Disease.
4
Duchmann R et al. Clin Exp Immunol 1995;102:448–455.
5
Mow WS et al. Gastroenterology 2004;126:414–424.
6
Neurath MF et al. Nat Rev Immunol 2014;14:329-342.
7
Sartor RB. Nat Clin Pract Gastroenterol Hepatol 2006;3:390–407.
8
Melmed GY et al. Nat Rev Gastroenterol Hepatol 2010;7:110–117.
9
Tato CM et al. Nature 2006;441:166–168.
10
Toussirot E. Inflamm Allergy Drug Targets 2012;11(2):159–68.
11
Sandborn W, et al. AIBD 2015:Abstract O-0001.
12
Feagan B, et al. UEGW 2015:Abstract UEG15-LB-5668.
2
March 2016
PHEM/IMM/0216/0003