title: 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-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin 4 (IL-4), IL-10, macrophage inflammatory protein-1alpha (MIP-1alpha), 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-1alpha, IP-10, and MIG mRNA compared with that in uninfected females, and expression of IL-10 and MIP-1alpha was significantly greater than that detected in infected male mice (P < or = 0.05). At 3 months after infection, cecal lesion scores were significantly (P < or = 0.05) increased in female and male mice compared with uninfected controls, and infected female mice had significantly (P < or = 0.05) higher cecal lesion scores than did infected male mice. In addition, infected females had significant (P < or = 0.05) increases in cecal IFN-gamma, TNF-alpha, IL-10, MIP-1alpha, IP-10, and MIG mRNA values compared with values in uninfected females and infected males, and male mice had significant (P < or = 0.05) increases in cecal TNF-alpha 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.
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine, 1600 East Rollins Road, University of Missouri, Columbia, Missouri 65211, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Livingston
authors.forename: Mathew H
authors.initials: MH
authors.lastname: Myles
authors.forename: Beth A
authors.initials: BA
authors.lastname: Livingston
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Criley
authors.forename: Craig L
authors.initials: CL
authors.lastname: Franklin
mesh_terms: D000818:Animals; D002432:Cecum; D005260:Female; D016481:Helicobacter Infections / Q000473:pathology* / Q000503:physiopathology*; D044923:Helicobacter hepaticus / Q000235:genetics / Q000302:isolation & purification; D007249:Inflammation / Q000382:microbiology / Q000473:pathology; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008815:Mice, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics