Low-grade inflammation plays a pivotal role in gastrointestinal dysfunction in irritable bowel syndrome

Abstract

The pathogenesis of irritable bowel syndrome (IBS) is considered to be multifactorial and includes psychosocial factors, visceral hypersensitivity, infection, microbiota and immune activation. It is becoming increasingly clear that low-grade inflammation is present in IBS patients and a number of biomarkers have emerged. This review describes the evidence for low-grade inflammation in IBS and explores its mechanism with particular focus on gastrointestinal motor dysfunction. Understanding of the immunological basis of the altered gastrointestinal motor function in IBS may lead to new therapeutic strategies for IBS.

Inflammation as a Potential Therapeutic Target in IBS

“…More and more data sustain the hypotheses of a low-grade inflammation in IBS [65][66][67]. The fine line between normal to a pathological inflammatory response is still difficult to set.…”

“…The fine line between normal to a pathological inflammatory response is still difficult to set. There is a low-grade inflammation of the gut that has been already acknowledged and literature data supports the putative role of the low-grade inflammation in IBS [65][66][67][68]. Several articles addressed this issue, some authors investigated tissue samples [23], while others assessed blood or stool samples [69][70][71][72] in order to detect and determine the inflammation status in IBS patients.…”

Co-regulated Intestinal c-kit by Interleukin-17 and Interleukin-10 on Post-infectious Irritable Bowel Syndrome in Mice

“…Uncontrolled IL-17 responses can augment production of inflammatory factors including IL-1,IL-6,IL-8,TNF-α,GM-CSF, and MIP-2 [21,23], these cytokines were reported to be increased in the peripheral blood and intestinal mucosa of PI-IBS patients [22], and which would alter the gut physiology and host immunity and cause clinical symptoms [22,31]. IL-10, as a classical anti-inflammatory cytokines, reduces inflammation reaction through numbers of mechanisms: It can diminish the production of inflammatory mediators including IL-1β and IFN-γ in T cells and activated macrophages [12][13][14]; it also can reduce the antigen-presenting cells surface expression of major histocompatibility complex class II molecules, co-stimulating and adhesion molecules [15,16].…”

“…IL-10, as a classical anti-inflammatory cytokines, reduces inflammation reaction through numbers of mechanisms: It can diminish the production of inflammatory mediators including IL-1β and IFN-γ in T cells and activated macrophages [12][13][14]; it also can reduce the antigen-presenting cells surface expression of major histocompatibility complex class II molecules, co-stimulating and adhesion molecules [15,16]. Decreased IL-10 levels and uncontrolled IL-17 in this study may hold a low-grade inflammation mode undetected by pathological examination [22,31]. Meanwhile, mucosal acute inflammation of the gut resulted in loss of ICC function because of structural injury and loss of c-kit positivity [32].…”

Chlamydiae in Gastrointestinal Disease

“…Despite its abundance the cause of IBS has remained unclear. It has long been considered a psychosomatic disorder but a number of studies have reported signs of immune activation with increased numbers of lymphocytes, activated macrophages or mast cells in mucosa biopsies from the small bowel or the large bowel (Akiho et al, 2011). We investigated full-thickness biopsies from the jejunum of 10 patients with IBS and found increased numbers of mucosal lymphocytes in 4/10 patients (Törnblom et al, 2002).…”