cholecystokinin and Trichinellosis

Gastrointestinal inflammation reduces food intake but the biological mechanisms explaining suppressed feeding during inflammation are unknown. We have used a model of upper gut infection (Trichinella spiralis in the mouse) to study the effect of inflammation on food intake, and explored the role of a key enteroendocrine cell (EEC) in the regulation of feeding by the immune response.. Food intake of NIH mice infected with the intestinal nematode Trichinella spiralis was measured. Duodenal cholecystokinin (CCK) cells were counted. Plasma CCK was measured. Infected mice were treated with a specific CCK1 receptor antagonist, and food intake reassessed. The influence of the immune response on food intake and CCK was mechanistically examined by treating mice with CD4 or mast cell neutralising antibodies. The role of the T helper 2 response was further explored in mice genetically deficient for interleukin (IL)-4, IL-13, or IL-4Ralpha (receptor alpha subunit).. Food intake of infected mice was significantly reduced at the temporal peak of intestinal inflammation. CCK expressing EEC were upregulated in infected mice, and plasma CCK levels were increased. A CCK1 receptor antagonist restored the food intake of infected mice to a significant degree. Furthermore, suppression of food intake was completely abolished in the absence of CD4+ T lymphocytes or IL-4Ralpha.. The data show for the first time that intestinal inflammation results in reduced food intake due to upregulation of CCK. Moreover, following infection, food intake and CCK expressing cells are under the specific control of CD4+ T-cells, via release of IL-4 and IL-13.

Topics: Animals; Cell Count; Cholecystokinin; Cytokines; Disease Models, Animal; Duodenum; Eating; Enteroendocrine Cells; Feeding and Eating Disorders; Immunohistochemistry; Interleukins; Intestine, Small; Mast Cells; Mice; Mice, Inbred BALB C; Mice, Inbred Strains; Receptors, Cholecystokinin; Th2 Cells; Trichinella spiralis; Trichinellosis

Trichinella spiralis infection in rats induces hypermotility and an abnormal response to cholecystokinin (CCK) similar to motor disturbances observed in irritable bowel syndrome. Mast cell hyperplasia is also characteristic of this experimental model. The aim of our study was to correlate mast cell activity with the development of dysmotility and to demonstrate whether the mast cell stabilizer ketotifen [4-(1-methyl-4-piperidylidene)-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one fumarate] could prevent the development of intestine hypermotility. Sprague-Dawley rats were infected with T. spiralis and, 5 days after infection, treated with the mast-cell stabilizer ketotifen (10 mg/kg/day). Twelve days after infection, intestinal spontaneous motor activity and response to CCK were evaluated by means of strain-gauge transducers. Immunohistochemistry for rat mast cell protease II (RMCPII), cyclooxygenase (COX)-2, and inducible nitric-oxide synthase (iNOS) was performed in intestinal specimens. In addition, RMCPII and myeloperoxidase were determined in serum. Infected control rats showed hypermotility, mast cell hyperplasia, increased RMCPII levels, increased myeloperoxidase, and overexpression of COX-2 and iNOS. In contrast, ketotifen-treated rats showed spontaneous intestinal motility and CCK response similar to the noninfected control rats. Mast cell hyperplasia and RMCPII were reduced in ketotifen-treated rats. Inflammatory parameters were less modified by ketotifen, but those animals that received the longest ketotifen treatment showed a slight amelioration in these parameters. These results indicate that mast cells are implicated in the development of hypermotility. The treatment with ketotifen prevented hypermotility and mast cell hyperplasia and diminished mucosal mast cell activity.

Topics: Animals; Cell Count; Cell Size; Cholecystokinin; Chymases; Cyclooxygenase 2; Gastrointestinal Motility; Histamine H1 Antagonists; Immunohistochemistry; Inflammation; Intestinal Mucosa; Ketotifen; Male; Mast Cells; Nitric Oxide Synthase Type II; Peroxidase; Rats; Rats, Sprague-Dawley; Trichinella spiralis; Trichinellosis

Nerve growth factor (NGF) could be involved in the development of hyperalgesia as well as in nervous remodeling consequence of inflammation. Both dysmotility and increase of visceral sensitivity have been described in functional gastrointestinal disorders such as irritable bowel syndrome. Trichinella spiralis-infected rats show an exacerbated spontaneous motility and a significant increase of the excitatory response to cholecystokinin (CCK), both associated with a reversible inflammatory process and the hypertrophy of the muscle layers. In this study we determined the intestinal expression of NGF mRNA by polymerase chain reaction and NGF by enzyme-linked immunosorbent assay. We implanted serosal strain gauge transducers on duodenum, jejunum, and ileum of anesthetized Sprague-Dawley rats to record circular muscle contractions. The experimental protocol included the evaluation of intestinal spontaneous motor activity (SMA), the response to CCK-8, and the ascending contraction induced by electrical mucosal stimulation. This protocol was performed in healthy and infected nontreated rats, in healthy rats with an NGF antibody treatment (1.6 mg/rat i.p.), and in infected rats with the same treatment applied at 0 or 3 days postinfection. NGF and NGF mRNA levels in the bowel were increased during inflammation. Although anti-NGF treatments did not prevent or reverse inflammatory response, the treatment was effective in preventing the motor alterations induced by the T. spiralis infection, i.e., inhibited increased SMA, reversed altered response to CCK, and reversed in part exacerbated response to electrical stimulation.

Topics: Animals; Antibodies; Cholecystokinin; Electric Stimulation; Gastrointestinal Motility; Intestine, Small; Male; Movement; Nerve Growth Factor; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transcription, Genetic; Trichinella spiralis; Trichinellosis

The objective of this study was to test the hypothesis that enteric parasites affect pancreatic secretion in their host. Pancreatic bicarbonate and protein outputs were studied in dogs with gastric and pancreatic fistulas to determine the secretory response to exogenously administered secretin and cholecystokinin and to intraduodenal stimulation with hydrochloric acid and sodium oleate to release endogenous hormones. Bicarbonate and protein concentrations in pancreatic juice were measured prior to infection with Trichinella spiralis and at various periods during primary and secondary infections. Dose-related increases in secretory activity were observed in uninfected hosts in response to all stimuli. Infected dogs responded like controls to exogenous hormones, but showed reduced secretion under duodenal stimulation during the 1st wk of primary infection. This altered response returned to normal 3 wk after primary infection and did not occur following secondary infection. Results support the conclusion that reduced pancreatic secretion is associated with enteric parasitism and is due to a defect in hormone release or in the supply of hormone available for release.

Topics: Animals; Bicarbonates; Cholecystokinin; Dogs; Hydrochloric Acid; Oleic Acids; Pancreas; Proteins; Secretin; Trichinellosis