Partial protection against dextran sodium sulphate induced colitis in histamine-deficient, histidine decarboxylase knockout mice.

Abstract

OBJECTIVES:

Chemically induced mucosal inflammation in animal models is a suitable tool for studying factors in the pathogenesis of inflammatory bowel disease. The aim of this study was to determine whether absence of histamine has an effect on the development of experimental colitis.

METHODS:

Histamine-deficient, histidine decarboxylase (HDC) knockout Balb/c mice and genetically identical control animals with intact HDC were studied. Colitis was induced by the administration of 2% dextran sodium sulphate in drinking water. Mice were killed after 5 days and disease activity assessed by clinical, histologic, and immunohistologic parameters. Bacterial components of stool were examined.

RESULTS:

Clinical disease activity was higher in the mice with intact HDC (disease activity index, 2.21) than in the histamine-deficient knock-out mice (1.88). Histologic findings were similar in the two groups. On day 5, the inflammation score of the HDC sufficient group was 5.25 (+/-1.055) and the crypt score was 5.00 (+/-1.128). The scores in the HDC knock-out group were 4.667 (+/- 0.707) and 4.667 (+/- 0.86), respectively. There was a significant difference in the number of interleukin (IL-10)-producing lymphocytes in colon mucosa. Large numbers of IL-10-positive lymphocytes were observed in wild type mice both those with DSS induced colitis and untreated controls. Only sporadic IL-10 positivity was found in histamine-deficient mice. Significant differences were found in the composition of the fecal bacterial flora between the two groups.

CONCLUSION:

The reduced number of IL-10-positive lymphocytes in the intestinal mucosa of histamine-deficient, histidine decarboxylase knockout mice and the altered fecal bacterial flora in these animals suggest that histamine may play a role in the pathophysiology of inflammation in the colon of normal animals by upregulating local IL-10 production and stimulating a local shift to Th2 response.

• Authors: László Bene, Zoltán Sápi, Attila Bajtai, Edit Buzás, Anna Szentmihályi, András Arató, Zsolt Tulassay, András Falus
• Journal: Journal of pediatric gastroenterology and nutrition (J Pediatr Gastroenterol Nutr) Vol. 39 Issue 2 Pg. 171-6 (Aug 2004) ISSN: 0277-2116 [Print] United States
• PMID: 15269623 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-10
• Histamine
• Dextran Sulfate
• Histidine Decarboxylase

Topics

• Animals
• Colitis (chemically induced, immunology, pathology, prevention & control)
• Dextran Sulfate (administration & dosage, adverse effects)
• Feces (microbiology)
• Histamine (deficiency)
• Histidine Decarboxylase (deficiency)
• Immunohistochemistry
• Interleukin-10 (biosynthesis)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Random Allocation
• Severity of Illness Index
• Up-Regulation