Interleukin-10 and Interleukin-10–Receptor Defects in Inflammatory Bowel Disease

Shah, Neil; Kammermeier, Jochen; Elawad, Mamoun; Glocker, Erik-Oliver

doi:10.1007/s11882-012-0286-z

Cited by 92 publications

(62 citation statements)

References 61 publications

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“…While genetic risk is an important factor in IBD and can influence the assemblage of gut microbes in individuals, it is not likely to be sufficient in causing disease except in rare cases of aggressive, early-onset IBD such as the disease caused by deficiency of IL-10 or the IL-10 receptor (17). This partial role for genetics is highlighted by the concordance rate for CD between monozygotic twins, which is between 35% and 58%, while that for UC is only 16% to 18.5% (18)(19)(20).…”

Section: R E V I E W S E R I E S : G U T M I C R O B I O M Ementioning

confidence: 99%

The microbial basis of inflammatory bowel diseases

Dalal¹,

Chang²

2014

J. Clin. Invest.

177

109

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Inflammatory bowel diseases (IBD) are chronic, progressive diseases characterized by aberrant immune responses to environmental and gut microbial triggers in genetically susceptible hosts. Clinical, genetic, and experimental data support the role of gut microbes in causing and sustaining these diseases. Our understanding of IBD has changed dramatically as the result of advances in cultivation-independent approaches and computational platforms for the analysis of large data sets. However, investigations relevant to clinical observations and the natural history of the diseases will be essential for the development of microbial, genetic, and biological metrics that may be used to individualize assessment of risk and improve clinical outcomes in IBD.

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Section: R E V I E W S E R I E S : G U T M I C R O B I O M Ementioning

confidence: 99%

The microbial basis of inflammatory bowel diseases

Dalal¹,

Chang²

2014

J. Clin. Invest.

177

109

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“…Therefore TGF-β1 may be a common link between the therapeutic effect of conditioned medium and administered MSCs in vivo . Additionally, interleukin (IL)-10, which is theorized to be a target in the amelioration of enterocolitis 57) , was elevated in the intestine and serum after MSC treatment of experimental colitis 37,53,58) . However, there is no evidence of IL-10 secretion by unstimulated MSCs in culture 59,60) .…”

Section: Immunomodulationmentioning

confidence: 99%

Mesenchymal stem cells for the treatment of inflammatory bowel disease: from experimental models to clinical application

Stavely

Sakkal

Stojanovska

et al. 2014

Inflammation and Regeneration

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AustraliaInflammatory Bowel Disease (IBD) is a highly debilitating and potentially fatal idiopathic disorder of the intestinal tract which is exceedingly prevalent in westernized society; however there is concern of an IBD epidemic in Asia due to increasing incidence rates. There is no cure for IBD with current treatments limited by their inefficacy, toxicity and adverse side-effects; thus necessitating the search for novel therapies. In the past decade mesenchymal stem cells (MSCs) have become attractive candidates for the cellular based therapy of IBD. MSCs are easily isolated and expanded from adult bone-marrow and adipose tissue; they possess unique therapeutic characteristics including the ability to home to sites of tissue damage and inflammation, facilitate tissue repair and modulate the immune system. The administration of MSCs in animal models of experimental colitis and clinical trials of fistulising and luminal Crohn's disease have yielded promising results, however an unequivocal therapeutic mechanism remains elusive. This review will explore the clinical application of MSCs in IBD and current evidence from experimental models of colitis elucidating their potential to ameliorate intestinal inflammation.Rec .The cause of IBD is unknown but concordant twin studies have revealed that the development of IBD is likely to require a multi-genetic predisposition and an environmental . The clinical application of MSCs in CD and evidence for the possible mechanisms elucidating their potential to regenerate intestinal epithelium and reduce inflammation in experimental models of colitis will be reviewed. Efficacy of MSCs in Clinical TrialsClinical trials using MSCs for the treatment of CD fistulae and luminal inflammation have demonstrated that MSC therapy in IBD is both efficacious and feasible (summarised in . Furthermore, sustained closure of fistulae has been achieved in 88-100% of subjects 8-12 months after a course of MSC therapy 26,28) ; however these effects are relatively transient given that only 58% of subjects maintain closure after 3 years 29) . This suggests that repeated treatment may be required to maintain the therapeutic benefits of MSC therapy.While autologous and allogeneic AT-MSCs have both demonstrated efficacy in the healing of fistulae, further evidence is required to determine long-term immune tolerance in patients with repeated allogeneic MSC exposure.Bacterial contamination has posed a problem in the expansion of autologous MSCs in the past causing delay in treatment 24,30) . If allogeneic MSCs are determined to be equally efficacious, pre-prepared sources for treatment could prevent such setbacks.One clinical trial has determined that MSCs were as effective in treating fistulae of cryptoglandular origin as they were for fistulae resultant of CD 32,33) . In a study

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“…To keep these proinflammatory activities under control and to prevent tissue damage, a powerful anti-inflammatory counterpart like IL-10 is required (Figure 26.2). 30 The role of IL-10 as a key anti-inflammatory cytokine has been known for a long time. In 1991, IL-10 was demonstrated to control the release of TNF and reactive oxygen intermediates of LPS challenged murine macrophages, 31 and mice lacking either the IL-10R2 subunit of IL-10R or functional IL-10 come down with severe enterocolitis.…”

Section: Il-10 Receptor Deficiency/il-10 Deficiencymentioning

confidence: 99%

“…Pathogenic mechanisms of IL-10 and IL-10R deficiencies 30. Compromised signaling through the IL-10 receptor prevents an important anti-inflammatory feedback signal in times of inflammation.…”

mentioning

confidence: 99%