Background: Inflammatory bowel disease (IBD) is a group of intestinal disorders characterised by
chronic relapsing inflammation of the small intestine and colon. IBD manifests as either ulcerative colitis or
Crohn’s disease and increases the risk of developing colorectal cancer.
Methods: Here, we have reviewed current treatment regimen for IBD utilising anti-inflammatory drugs, immune
system suppressors and antibiotics or a combination of these. However, these therapeutics lead to a number of
adverse effects, remission or significant non-responsiveness creating an urgent need to develop potent drugs with
novel mechanisms of action for IBD.
Results: The inflammasome is a multiprotein complex that assembles to a key innate immune system signalling
platform and is involved in the pathogenesis of inflammatory and autoimmune diseases. A number of investigations
show that the NLRP3 inflammasome recognizes microbial and cell stress components and serve as a platform
for caspase-1 activation and pro-inflammatory cytokine IL-1β, IL18 maturation. Although the exact aetiology
of IBD is unknown, uncontrolled NLRP3 Inflammasome activation has shown to play a major role in the
chronic intestinal inflammation and mature IL-1β and IL18 are consistently associated with increased colitis and
colitis associated colorectal cancer development.
Conclusion: In this review, we discuss the experimental NLRP3 inhibitors that have been investigated in IBD
experimental models. The potential mechanism of action of these inhibitors such as inhibiting NF-κB activation
and decreasing mitochondrial reactive oxygen species are discussed in detail. We further expand the controversial
role of NLRP3 in IBD and future issues that might arise from the long term use of NLRP3 inhibitors in IBD therapy.