Protection against Helicobacter pylori infection in the Mongolian gerbil after prophylactic vaccination.

Vaccines against Helicobacter pylori could circumvent the problem of increasing antibiotic resistance. They would be particularly useful in developing countries, where re-infection rates are high following standard eradication regimes. The Mongolian gerbil is a good model for H. pylori infection, as the gastric pathology induced by infection is similar to that in humans. The H. pylori-induced inflammatory response in gerbils is considerably greater than in murine models. The aim of this study was to determine if gerbils could be vaccinated against H. pylori. Mongolian gerbils were vaccinated orally with an H. pylori whole cell sonicate preparation and cholera toxin adjuvant. Vaccinated gerbils and controls were challenged with the autologous H. pylori strain 42GX. All infection, and cholera toxin, control gerbils were H. pylori positive 6 weeks post-challenge. By contrast, a significant degree of protection was demonstrated in vaccinated gerbils. Only two of 10 of gerbils were H. pylori positive (P<0.001). Protection was associated with increased serum H. pylori IgG antibodies. Protected gerbils had histologically normal gastric mucosa and, in contrast to mice, no post-immunisation gastritis was evident. In the control groups, the degree of inflammation was variable, with some of the animals having corpus gastritis and corpus mucous metaplasia. The levels of gastric IL-12p40 and IFNgamma transcripts were significantly decreased in vaccinated animals compared to infection and cholera toxin controls (P<0.01). Gastric IL-10 and TGFbeta transcripts were found only at relatively low levels. These results demonstrate that Mongolian gerbils can be successfully vaccinated against H. pylori and protected from H. pylori-induced pathology.

Inflammation in acne scarring: a comparison of the responses in lesions from patients prone and not prone to scar.

BACKGROUND: Many patients with inflammatory acne suffer from significant scarring, which is disfiguring and difficult to treat. A cell-mediated immune response is considered to be involved in the pathogenesis of acne, although the extent of this response has been found to differ among patients. OBJECTIVE: To assess whether there were differences in the cell-mediated immune responses at different time points in inflamed lesion development and resolution in patients who were prone (S patients) and those with the same degree of inflamed acne who were not prone (NS patients) to develop scarring. METHODS: Cellular and vascular markers were investigated using standard immunohistochemical techniques on biopsies of inflamed lesions of known duration, i.e. < 6 h (n = 14), 24 h (n = 14), 48 h (n = 10), 72 h (n = 10) and 6-7 days (n = 11) from the backs of acne patients. RESULTS: In early lesions from NS patients there was a large influx of CD4+ T cells, macrophages and Langerhans cells with a high number of cells expressing HLA-DR. Also there was significant angiogenesis and vascular adhesion molecule expression. Cell recruitment peaked in 48 h lesions, after which leucocyte numbers decreased and vascular activity returned to normal. Of the T cells, only 50% were memory/effector (CD45RO+) and naive (CD45RA+) cells, while the remainder were unclassified (CD45RO-, CD45RA-). In early lesions from S patients, CD4+ T cell numbers were smaller, although a high proportion were skin homing memory/effector cells. Langerhans cell numbers and cellular HLA-DR expression were low, while numbers of macrophages, blood vessels and vascular adhesion molecules were high. In resolving lesions angiogenesis remained high, with a further influx of macrophages and skin homing memory/effector cells and increased cellular HLA-DR expression. CONCLUSIONS: The cellular infiltrate was large and active with a greater nonspecific response (few memory T cells) in early lesions of NS patients, which subsided in resolution. In contrast, a predominantly specific immune response was present in S patients, which was initially smaller and ineffective, but was increased and activated in resolving lesions. Such excessive inflammation in healing tissue is conducive to scarring and suggests that the use of topical anti-inflammatory treatments would be appropriate for these patients.

The effect of gender on Helicobacter felis-mediated gastritis, epithelial cell proliferation, and apoptosis in the mouse model.

The murine Helicobacter felis model has been extensively used to investigate the importance of host factors in the development of chronic gastritis. The effect of gender in this murine model is unknown. Male and female C57BL/6J mice were infected with H felis for up to 1 year. At 4, 8, 19, 36, and 52 weeks post-infection, gastric histopathology, epithelial cell proliferation, and apoptosis were examined and compared with age- and gender-matched controls. In female mice, infection with H felis resulted in an earlier onset of chronic gastric inflammation, epithelial hyperplasia, and oxyntic cell loss than males. In females, there was a trend towards increased gastric pathology compared with males, with long-term-infected female mice having significantly greater (p < 0.05) chronic inflammation than male mice. The histopathological differences in male and female mice did not relate to the density of H felis infection. Female mice infected with H felis had significantly increased gastric epithelial cell proliferation in the cardia and corpus at both 8 and 52 weeks post-infection (p < 0.05). Epithelial cell apoptosis in the glandular mucosa of the corpus at 36 and 52 weeks post-infection was significantly increased (p < 0.05) in female mice compared with uninfected gender controls. In contrast, there was no significant increase in epithelial cell proliferation or apoptosis in any area of the stomach at any time point after H felis infection in male mice. These results demonstrate that there are gender differences in the gastric inflammatory and epithelial response to H felis in the murine model. The functional importance of gender should be considered in future murine studies on H felis- and H pylori-induced chronic gastritis.