Q J Med 2003; 96: 870-871
© 2003 Association of Physicians
Correspondence |
Plasma cholecystokinin concentrations are elevated in acute upper gastrointestinal infections
Sir,Proximal gastrointestinal infections such as giardiasis are prevalent throughout the developing world, and cause morbidity in travellers from non-endemic areas. In giardiasis, the severity of symptoms (nausea, anorexia and diarrhoea) does not correlate well to the degree of histological abnormality. Eating is a frequent trigger for symptoms in gut infections. Enteroendocrine cells (EEC) respond to nutrients in the gut lumen by secreting signalling molecules such as cholecystokinin (CCK), which stimulate receptors on vagal afferent nerves to signal to the brain.
A Professor of Gastroenterology returned from China with nausea, anorexia, bloating and steatorrhoea. He then took part as a prescheduled ‘healthy volunteer’ in a research study, studying plasma CCK by radioimmunoassay1 after a test meal. His fasting CCK was 4.0 pM, compared with 1.0 ± 0.3 pM in healthy controls. Fifteen minutes post-prandially, his levels rose to 33.0 pM, compared with 8.0 ± 0.9 pM in controls. After a diagnosis of giardiasis, he was treated with tinidazole, and symptoms improved rapidly. CCK responses repeated 3 and 6 months later were normal.
We investigated whether this occurred more widely. Six patients with symptomatic acute upper GI (infection group) were studied. Subjects were aged 19–51 years (mean 35 ± 15); three were female. Diagnosis of Giardia lamblia infection was made in five patients and non-01 Vibrio infection in one. Eleven healthy controls, aged 21–45 years (mean 28 ± 7), six males, were also studied. A soup test meal was given: blood samples were taken for CCK fasted and 15 and 60 min post-prandially. Elevated fasted and fed CCK responses were found in all patients (Figure 1); all reported nausea and anorexia.
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This is the first demonstration that plasma CCK concentrations are elevated during symptomatic acute upper gut infection. Normally, CCK co-ordinates the foregut response to nutrients, and inhibits further food intake. Infused in high dose intravenously to healthy subjects, CCK produces nausea and abdominal discomfort,2 symptoms comparable to those during infection. We propose that endogenous CCK hypersecretion in infection directly contributes to symptom generation.
CCK could present a therapeutic target. However an innate, adaptive response that inhibits oral intake may be appropriate, not pathological, and may be protective at a time of gut inflammation or environmental contamination. Moreover, CCK decreases bacterial translocation3 and increases luminal IgA secretion.4
Acute infections resolve, but symptoms do not always disappear. Rectal 5-HT cell hyperplasia was recently described in post-Campylobacter irritable bowel syndrome,5 suggesting that persistent EEC upregulation may underpin chronic symptoms in a subset of patients following gut infections. Our work adds to evidence that EEC dysfunction may influence symptom production.
Section of Gastrointestinal Science University of Manchester Physiological Laboratory University of Liverpool Department of Infectious Diseases North Manchester General Hospital UK
References
1. McLaughlin JT, Luca MG, Jones MN, et al. Fatty acid chain length determines cholecystokinin secretion and effect on human gastric motility. Gastroenterology 1999; 116:46–53.[CrossRef][Web of Science][Medline]
2. Chua ASB, Dinan TG, Rovati LC, et al. Cholecystokinin hyperresponsiveness in dysmotility-type non-ulcer dyspepsia. Ann NY Acad Sci 1994; 713:298–9.[Web of Science][Medline]
3. Wang X, Soltesz V, Axelson J, et al. Cholecystokinin increases small intestinal motility and reduces enteric bacterial overgrowth and translocation in rats with surgi-cally induced acute liver failure. Digestion 1996; 57:67–72.[Web of Science][Medline]
4. Freier S, Eran M, Faber J. Effect of cholecystokinin and of its antagonist, of atropine, and of food on the release of immunoglobulin A and immunoglobulin G specific antibodies in the rat intestine. Gastroenterology 1987; 93:1242–6.[Web of Science][Medline]
5. Spiller RC, Jenkins D, Thornley JP, et al. Increased rectal mucosal enteroendocrine cells, T lymphocytes and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut 2000; 47:804–11.
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