Increased TLR2 expression on blood monocytes in irritable bowel syndrome patients.

OBJECTIVES: The understanding of the mechanisms for increased immune activation in subgroups of patients with irritable bowel syndrome (IBS) is incomplete. We hypothesized that monocytes are more activated in patients with IBS than in the healthy population. We therefore examined activation phenotype and cytokine secretion of blood monocytes. METHODS: Blood samples from 74 patients with IBS and 30 controls were obtained. The activation phenotype of CD11cCD14 monocytes and cytokine secretion in serum and in peripheral blood mononuclear cells cultured with or without lipopolysaccharide was determined. Gastrointestinal and psychological symptom severity and quality of life were assessed using validated questionnaires. RESULTS: Monocytes from patients demonstrated an increased expression of toll-like receptor (TLR) 2, whereas the expression on monocytes of TLR4, HLA-DR, CD40, CD80 and CD86 was comparable in patients and controls. The expression of activation markers on monocytes did not correlate with gastrointestinal or extracolonic symptom severity, but the expressions of TLR2, HLA-DR and CD86 were associated with less severe psychological symptoms and better social and physical well-being. Cytokine secretion in serum and peripheral blood mononuclear cell cultures was comparable in patients and controls. A subgroup of patients (15%) who had TLR2 and HLA-DR expression intensity above the level seen in controls reported less severe psychosocial symptoms. CONCLUSION: Patients with IBS have increased expression of TLR2 on monocytes and the activation level on monocytes correlates with less severe psychological symptoms and better quality of life. Thus, our data implicate less importance of psychosocial factors and increased importance of immunological parameters for symptom generation in a subgroup of patients with IBS.

T-cell activation in patients with irritable bowel syndrome.

OBJECTIVES: Irritable bowel syndrome (IBS) has been found to be associated with low-grade immune activation in a subset of patients. We therefore investigated blood and colonic T-cell activity in IBS patients. METHODS: Blood samples were initially obtained from 74 IBS patients and 30 controls. Supplementary blood samples, to confirm data, were taken from another cohort (26 patients and 14 controls). In addition, colonic biopsies were taken from a third cohort (11 patients and 10 controls). Peripheral blood and colonic mononuclear cells were stimulated with anti-CD3/CD28 antibodies. Proliferation, cytokine secretion, and T-cell phenotype were investigated. IBS symptom severity was assessed. RESULTS: IBS patients displayed an activated phenotype with increased frequencies of blood T cells expressing CD69 and integrin beta7/HLA-DR. Anti-CD3/CD28-stimulated blood and colonic T cells from IBS patients proliferated less than T cells from controls. IBS patients had an increased polyclonally stimulated T-cell secretion of IL-1beta, which also weakly correlated with increased bowel habit dissatisfaction. Furthermore, despite normal frequencies of CD25high T cells in the blood of IBS patients, lower blood CD25high T-cell frequencies were modestly correlated with more bowel habit dissatisfaction and increased total IBS symptom severity. CONCLUSIONS: IBS patients have an increased frequency of activated T cells, demonstrated by the expression of activation markers and reduced proliferation in response to restimulation in vitro. The increased level of T-cell activation is consistent with the hypothesis of low-grade immune activation in IBS and may also be involved in symptom generation in IBS.