First observations with dextran sulphate induced intestinal inflammation in the histamin deficient, histidine decarboxylase knockout mice

Objectives: The aim of the study was to elucidate whether the lack of histamine has an effect on the development of colitis.

Methods: Histamine deficient, histidine decarboxylase (HDC) knockout Balb/c mice and control animals with the same background but with intact HDC were studied. The inflammation was induced by the administration of 2% dextran sodium sulphate in the drinking water. The mice was sacrified after five days in order to examine the disease activity by clinical, histological and immunohistological parameters. The bacterial components of stool were examined by bacteriological methods.

Results: The clinical activity was moderately higher in the control group (disease activity index: 2.21) compared to the gene targeted, histamine deficient group (1.88), the histological findings, however did not reflect significant differences. The inflammation scores were in the control group 5.25 (±1.055); the crypt score: 5.00 (±1.128) at day five, while 4.667 (±0.707) and 4.667 (±0.86) in the HDC-/- group, respectively. A sharp difference was detected in the frequency of interleukin (IL-10) producing lymphocytes; while relatively large number of IL-10 positive lymphocytes were observed in wild type inflamed and normal colonic tissue, only very sporadic IL-10 positivity was found in histamine deficient mice. Major differences were found in the composition of the fecal bacterial flora, as well.

Conclusion: The highly reduced number of IL-10 positive lymphocytes in the intestinal mucosa of histamine deficient, histidine decarboxylase knockout mice and altered fecal bacterial flora suggest that histamine plays an important role in the pathophysiology of gut tissue.