Sex Influence on Chronic Intestinal Inflammation in Helicobacter hepaticus-Infected A/JCr Mice
Abstract:Helicobacter hepaticus is a bacterial pathogen of mice that has been reported to cause chronic intestinal inflammation in A/JCr, germfree Swiss Webster, and immunodeficient mice. To the authors' knowledge, the influence of sex on development of chronic intestinal inflammation in H. hepaticus-infected mice has not been investigated. The purposes of the study reported here were to determine whether severity of intestinal inflammation differs between male and female A/JCr mice chronically infected with H. hepaticus and to characterize the mucosal immune response in these mice. The cecum of male and female A/JCr mice infected with H. hepaticus for 1 month and 3 months was objectively evaluated histologically for intestinal disease. Also, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was done to measure interferon-gamma (IFN-), tumor necrosis factor-alpha (TNF-α), interleukin 4 (IL-4), IL-10, macrophage inflammatory protein-1α (MIP-1α), interferon-inducible protein of 10 kDa (IP-10), and monokine induced by gamma interferon (MIG) mRNA values in the cecal tissue of these mice. Significant differences in cecal lesion scores were not present at 1 month after infection. However, infected female mice had significantly up-regulated expression of cecal IL-10, MIP-1α, IP-10, and MIG mRNA compared with that in uninfected females, and expression of IL-10 and MIP-1α was significantly greater than that detected in infected male mice (P ≤ 0.05). At 3 months after infection, cecal lesion scores were significantly (P ≤ 0.05) increased in female and male mice compared with uninfected controls, and infected female mice had significantly (P ≤ 0.05) higher cecal lesion scores than did infected male mice. In addition, infected females had significant (P ≤ 0.05) increases in cecal IFN-, TNF-α, IL-10, MIP-1α, IP-10, and MIG mRNA values compared with values in uninfected females and infected males, and male mice had significant (P ≤ 0.05) increases in cecal TNF-α and IL-10 mRNA values compared with those for male control mice. These data indicate that, in H. hepaticus-infected A/JCr mice, females develop more severe intestinal inflammation than do males, and the chronic mucosal inflammation is polarized toward a Th1 response that is not down-regulated by increased activity of IL-10. We propose that H. hepaticus-infected A/JCr mice will serve as a good animal model with which to study the influence of sex on bacterial-induced mucosal inflammation.
Document Type: Research Article
Affiliations: Department of Veterinary Pathobiology, College of Veterinary Medicine, 1600 East Rollins Road, University of Missouri, Columbia, Missouri 65211
Publication date: June 1, 2004
Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.
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