Immune activation in patients with irritable bowel syndrome.
OBJECTIVE
We set out to test the hypothesis that irritable bowel syndrome (IBS) is characterized by an augmented cellular immune response with enhanced production of proinflammatory cytokines. We further aimed to explore whether symptoms and psychiatric comorbidity in IBS are linked to the release of proinflammatory cytokines.


METHODS
We characterized basal and Escherichia coli lipopolysaccharide (LPS)-induced cytokine production in peripheral blood mononuclear cells (PBMCs) from 55 IBS patients (18 mixed-, 17 constipation-, 20 diarrhea-predominant) and 36 healthy controls (HCs). PBMCs were isolated by density gradient centrifugation and cultured for 24 hours with or without (1 ng/mL) LPS. Cytokine production (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, and IL-6) was measured by enzyme-linked immunosorbent assay. Abdominal symptoms and psychiatric comorbidities were assessed by using the validated Bowel Disease Questionnaire and the Hospital Anxiety and Depression Scale.


RESULTS
IBS patients showed significantly (P < .017) higher baseline TNF-alpha, IL-1beta, IL-6, and LPS-induced IL-6 levels compared with HCs. Analyzing IBS subgroups, all cytokine levels were significantly (P < .05) higher in diarrhea-predominant IBS (D-IBS) patients, whereas constipation-predominant IBS patients showed increased LPS-induced IL-1beta levels compared with HCs. Baseline TNF-alpha and LPS-induced TNF-alpha and IL-6 levels were significantly higher in patients reporting more than 3 bowel movements per day, urgency, watery stools, and pain associated with diarrhea compared with patients without these symptoms (all P < .05). LPS-induced TNF-alpha production was associated significantly (r = 0.59, P < .001) with anxiety in patients with IBS.


CONCLUSIONS
Patients with D-IBS display enhanced proinflammatory cytokine release, and this may be associated with symptoms and anxiety.
Liebregts
Tobias
T
Department of Gastroenterology and Hepatology, University of Adelaide, Royal Adelaide Hospital, South Australia, Australia.
Adam
Birgit
B
Bredack
Christoph
C
Röth
Alexander
A
Heinzel
Susanne
S
Lester
Sue
S
Downie-Doyle
Sarah
S
Smith
Eric
E
Drew
Paul
P
Talley
Nicholas J
NJ
Holtmann
Gerald
G
D000328:Adult; D001007:Anxiety / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D003863:Depression / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D018836:Inflammation Mediators / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D043183:Irritable Bowel Syndrome / Q000276:immunology* / Q000378:metabolism / Q000523:psychology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; C508600:IL6 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha