Immune dysfunction in patients with functional gastrointestinal disorders

Abstract

There is increasing evidence for involvement of the immune system in functional gastrointestinal disorder (FGID), including onset after acute gastrointestinal infections, genotypes resulting in altered cytokine expression and abnormal presence of immune cells. Our aim was to assess cellular and humoral immune responses in (i) FGIDs, compared to healthy subjects and (ii) acute vs unspecified onset FGIDs. Lymphocytic [interleukin (IL)-5, IL-10, IL-13 and interferon gamma (IFN-gamma)] and monocytic [IL-10, IL-12, tumour necrosis factor (TNF)-alpha] cytokine production was characterized at baseline and after stimulation with phytohemagglutinine and anti-CD28 or lipopolysaccharide (LPS) in controls (n = 32), irritable bowel syndrome (IBS) (n = 30), functional dyspepsia (FD) (n = 23) and non-cardiac chest pain (NCCP) (n = 15). Serum IL-6 and IL-10 concentrations were compared, and the immunophenotype was assessed using fluorescent-activated cell sorter. Findings were compared for acute vs unspecified onset FGID. Compared to controls, stimulated lymphocyte expression of IL-5 and IL-13 was enhanced in IBS, FD and NCCP (all P < 0.05). Conversely, the stimulated monocytic IL-12 and lymphocytic IL-10 expression were reduced in IBS and FD, while IFN-gamma expression was also reduced in FD patients. Except for an increase in the numbers of CD3(+)CD45RA(+)CD45RO(+) cells, no distinct cellular profile was detected. Patients with a presumed acute onset of their symptoms had higher serum IL-10 levels and more CD3(+)CD45RA(+)CD45RO(+) cells, while TNF-alpha levels following stimulation with LPS were higher in FD patients reporting an acute onset. A shift towards a Th2 cytokine profile is present in FGID, while the cellular immunophenotype remains largely unchanged. Further research is indicated and could provide new therapeutic strategies for these disorders.

Review article: associations between immune activation, intestinal permeability and the irritable bowel syndrome

“…Cytokine assays have revealed no major changes in the basal levels of cytokines in IBS patients [31][32][33][34] with the exception of IL6 and IL8, which have been found to be moderately increased in some studies. 31,34,35 A decrease in the levels of the antiinflammatory cytokine IL10 has also recently been reported in children with IBS, 36 although this decrease was not observed in adults.…”

“…31,34,35 A decrease in the levels of the antiinflammatory cytokine IL10 has also recently been reported in children with IBS, 36 although this decrease was not observed in adults. 31,32 However, several studies that assessed the effect of immune challenges on cytokine production by peripheral blood mononuclear cells isolated from IBS patients have reported the abnormal secretion of both pro-and anti-inflammatory cytokines. 32,34,35,37,38 For example, IBS mononuclear cells released more tumour necrosis factor-a (TNF-a), IL1b and IL6 following exposure to lipopolysaccharides produced by Escherichia coli when compared with mononuclear cells isolated from healthy control patients.…”

Immune Activation in Irritable Bowel Syndrome: Can Neuroimmune Interactions Explain Symptoms?

“…Circulating B cells are also more likely to express the GI homing integrin β 7 in IBS patients compared with healthy subjects; however, numbers of B cells are unchanged in the descending colon ( Figure 1 and Table 2 ) ( 53,78,104 ). A greater proportion of B cells express the activation markers CD80 and CD86, and T-cell activation induces increased release of cytokines involved in B-cell activation in IBS compared with health ( 68,78 ).…”

“…A greater proportion of B cells express the activation markers CD80 and CD86, and T-cell activation induces increased release of cytokines involved in B-cell activation in IBS compared with health ( 68,78 ). Th e primary role of B cells is to produce antibodies (Ig) directed against antigen, and IgG-positive B cells are increased in the blood of IBS patients relative to healthy subjects ( 68 ).…”

Prevalence of Irritable Bowel Syndrome in Singapore and Its Association with Dietary, Lifestyle, and Environmental Factors

“…Koloski et al 21 thought that shorter duration of breast feeding, caesarean section, and exposure to pets may increase exposure to endotoxins and alter the gut microbiota which favor the development of IBS by tilting the balance of cytokines profile towards a T helper 2 response. 22 Animals like dogs and horses have been involved in animalassisted therapy in multiple chronic conditions. We often see dogs assisting people with various disabilities, and animals can also help in reduction of anxiety and depression, improvement in mood and development of social skills.…”