Does nicotine influence cytokine profile and subsequent cell cycling/apoptotic responses in inflammatory bowel disease?

Aldhous, Marian C.; Prescott, R. J.; Roberts, Simon; Samuel, Kay; Waterfall, Martin; Satsangi, Jack

doi:10.1002/ibd.20523

Cited by 29 publications

(23 citation statements)

References 72 publications

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“…In CD, nicotine mildly reduced apoptosis in response to PHA or in unstimulated cells. 70 Nicotine may act on the MAP kinase family and affect TNF-a through inhibition of nuclear factor kappa B signalling. 2 Loss of the intestinal mucosal barrier function may underlie the pathogenesis of IBD.…”

Section: 21mentioning

confidence: 99%

Review article: ulcerative colitis, smoking and nicotine therapy

Lunney

Leong

2012

Aliment Pharmacol Ther

119

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SummaryBackgroundSmoking is the best‐characterised environmental association of ulcerative colitis (UC). Smoking has been observed to exert protective effects on both the development and progression of UC.AimsTo examine the association between UC and smoking, possible pathogenic mechanisms and the potential of nicotine as a therapeutic agent in the treatment of UC.MethodsA literature search was conducted through MEDLINE, using the MeSH search terms ‘ulcerative colitis’ and ‘smoking’ or ‘nicotine’. Relevant articles were identified through manual review. The reference lists of these articles were reviewed to include further appropriate articles.ResultsUlcerative colitis is less prevalent in smokers. Current smokers with a prior diagnosis of UC are more likely to exhibit milder disease than ex‐smokers and nonsmokers. There is conflicting evidence for smokers having reduced rates of hospitalisation, colectomy and need for oral corticosteroids and immunosuppressants to manage their disease. Multiple potential active mediators in smoke may be responsible for these clinical effects, including nicotine and carbon monoxide, but the precise mechanism remains unknown. Nicotine has demonstrated variable efficacy in the induction of remission in UC when compared to placebo and conventional medicines. Despite this, the high frequency of adverse events limits its clinical significance.ConclusionsNicotine's application as a therapeutic treatment in ulcerative colitis is limited. Presently, it may be an option considered only in selected cases of acute ulcerative colitis refractory to conventional treatment options. This review also questions whether nicotine is the active component of smoking that modifies risk and inflammation in ulcerative colitis.

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Section: 21mentioning

confidence: 99%

Review article: ulcerative colitis, smoking and nicotine therapy

Lunney

Leong

2012

Aliment Pharmacol Ther

119

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“…Cigarette smoking, and more specifically nicotine, is known to have detrimental effects on the generation of proinflammatory cytokines in patients with CD [76,77], in keeping with the predominantly immunosuppressive effects of smoking on the immune response [78]. Recently, differential gene expression profiles have also been demonstrated in the colonic mucosa of smokers compared with nonsmokers with CD [79], but the significance of these findings is unclear.…”

Section: Lifestyle Factors May Influence Intestinal Barrier and Innate mentioning

confidence: 99%

Crohn’s disease as an immunodeficiency

Hayee

Rahman

Sewell

et al. 2010

Expert Review of Clinical Immunology

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The pathogenesis of Crohn's disease (CD) has widely been regarded as the consequence of a dysregulated T-cell-mediated response to intestinal microbes, and the majority of the worldwide research effort has focused on characterizing and treating the chronic inflammatory phase of the disease. However, recent molecular biological and clinical investigations indicate that CD is actually a primary immunodeficiency. At first counter-intuitive, the apparent paradox of a pathogenic innate immune defect can be linked mechanistically to the granulomatous chronic inflammation characteristic of the disease. Genome-wide association studies have corroborated the involvement of innate immune dysfunction in the pathogenesis of CD, but less than 20% of the heritable risk is accounted for. By contrast, in vitro and in vivo stimulation of the immune system has highlighted novel areas of interest that may lead to the development of targeted therapeutic and diagnostic tools. Keywordsbacteria; Crohn's disease; immunodeficiency; innate immunity; macrophage; neutrophil Established intestinal lesions in Crohn's disease (CD) contain a massive, mixed inflammatory cell infiltrate associated with a complex storm of cytokines in a selfperpetuating, chronic inflammatory response [1][2][3]. Most research to date has focused on the the immunological characteristics of established lesions and drawn inferences about their initiation. The predominance of a classically Th1-associated cytokine profile in these lesions led to the assumption that T lymphocytes were central to the initial pathogenesis. More recently, the role of regulatory (Treg) FoxP3 + and IL-23-induced responsive Th17-type T lymphocytes has gained popularity [2,4,5]. Treg cell populations are diminished in patients with CD [6] and, although the hypothesis of CD as an immunodeficiency does not necessarily exclude defects in T-cell function, to date, no convincing intrinsic (primary) defect has been identified to implicate these cells in the pathogenesis of human CD.The hypothesis that immunodeficiency underpins the development of CD seems, at first, to be in direct contrast with histological observations of established intestinal lesions and the † Author for correspondence: Tel.: +44 207 679 6170 Fax: +44 207 679 0967 b.hayee@nhs.net. Financial & competing interests disclosure The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Europe PMC Funders Group Association between immunodeficiency diseases & CDThere is a well-known and strong association between primary immunodeficiency disorders and non-infectious granulomatous intestinal inflammation. Chronic granulomatous disease (CGD), glycogen storage disease type 1b, leukocyte adhesion deficiency, Chediak-Higashi and Hermansky-Pudlak syndromes are all strongly associated with intestinal inflammation that is indistinguishable from CD [...

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“…Previously published human studies investigated distinct anatomical compartments (gut lavage fluid versus peripheral blood mononuclear cells versus colonic mucosa), which makes it difficult to draw general conclusions. [9][10][11][12] On the other hand, established animal models have several limitations to explore the effect of smoking on CD. First, most reports describe the effect of (sub)acute smoke exposure, whereas human smoking usually involves prolonged periods of smoke exposure.…”

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confidence: 99%

Cigarette smoking alters epithelial apoptosis and immune composition in murine GALT

Verschuere

Bracke

Demoor

et al. 2011

Laboratory Investigation

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Smokers have a twofold increased risk to develop Crohn's disease (CD). However, little is known about the mechanisms through which smoking affects CD pathogenesis. Especially Crohn's ileitis is negatively influenced by smoking. Interestingly, the ileum and, more in particular, the Peyer's patches in the terminal ileum are also the sites where the first CD lesions are found. Several chemokines are implicated in the pathogenesis, among which is the CCL20-CCR6 pathway. Here, we studied the gut-associated lymphoid tissue in C57BL/6 wild-type mice and in CCR6-deficient mice after exposure to air or cigarette smoke for 24 weeks. Apoptotic index of the follicle-associated epithelium overlying the Peyer's patches was evaluated. We found that chronic smoke exposure induced apoptosis in the follicle-associated epithelium. Furthermore, immune cell numbers and differentiation along with chemokine expression were determined in Peyer's patches. Important changes in immune cell composition were observed: total dendritic cells, CD4 þ T cells (including regulatory T cells) and CD8 þ T cells increased significantly after smoke exposure. The CD11b þ dendritic cell subset almost doubled. Interestingly, these changes were accompanied by an upregulated mRNA expression of the chemokines CCL9 and CCL20. However, no differences in the increase of dendritic cells were observed between wild-type and CCR6-deficient mice. Our results show that cigarette smoke exposure increases apoptosis in the follicle-associated epithelium and is associated with immune cell accumulation in Peyer's patches.

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Does nicotine influence cytokine profile and subsequent cell cycling/apoptotic responses in inflammatory bowel disease?

Abstract: Dysregulated cytokine profiles in UC and CD are associated with specific alterations in cell cycle responses; these effects may be modified by nicotine, and potentially by anticytokine therapies.

Cited by 29 publications

References 72 publications

Review article: ulcerative colitis, smoking and nicotine therapy

Review article: ulcerative colitis, smoking and nicotine therapy

Crohn’s disease as an immunodeficiency

Cigarette smoking alters epithelial apoptosis and immune composition in murine GALT

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