Interleukin-1β and transforming growth factor-β are associated with increased pathology in γ-interferon gene knockout mice infected with chlamydiae

T. Darville, J. Sikes, C. W. Andrews, D. M. Williams, R. G. Rank

Research output: Contribution to journalArticlepeer-review

Abstract

The components of the host response to chlamydial genital tract infection that cause tissue damage remain to be determined. Normal female C57 mice resolve chlamydial genital tract infection in 3 to 4 weeks, whereas C57 mice deficient in the interferon-γ gene (IFNγKO) develop a low grade persistent infection. Upon sacrifice, IFNγKO mice exhibit gross purulence in the uterine horns and severe fibrinous peritoneal disease likened to Fitz-Hugh-Curtis syndrome. Histopathological scoring of mesosalpingeal tissues from mice sacrificed on day 35 of infection reveal significantly increased inflammation and fibrosis in the IFNγKO mice compared to normal C57 mice (neutrophils:4+ vs. 1+; lymphocytes:3+ vs. 1+; fibrosis; 1+ vs. none). Endocervical secretions collected on interval days over the course of infection in the two groups reveal significant differences in levels of IL-1β and TGF-β determined by ELISA. IL-1β increases rapidly in both the normal and IFNγKO mice during the first week of infection, and then begins to decline in both groups. However, on days 14 through 35, IL-1β levels are significantly increased in the IFNγKO mice compared to normals with p = 0.04 by 2-way analysis of variance. Thus, IL-1β is present in increased amounts in the C57 IFNγKO mice compared to normals during the later days of infection, at a time when exudative neutrophils are noted to be significantly increased in the genital tract tissues. Assay for active TGF-β1 revealed a peak on day 7 in the normal C57 mice and then a fall to baseline by day 21. In the C57 IFNγKO mice, significant increases over baseline occurred on days 7, 21, and 28, and continued as late as day 40- Significantly higher amounts of active TGFβ1 were detected in the IFNγKO mice on days 28, and 40 (day 28 = 0.80 ± 0.08 vs. 0.09 ± 0.02 ng/mL; day 40 = 0.43 ± 0.07 vs. 0.05 ± 0.01 ng/mL). The late increase in TGFβ seen in the IFNγKO mice is likely in response to the continued presence of IL-1β and other proinflammatory mediators released in the face of a low grade persistent infection. But, despite the fact that TGFβ works to down-regulate the inflammatory response, its continued presence in excess may promote fibrosis and scarring as seen in the mesosalpingeal tissues of the IFNγKO mice.

Original languageEnglish (US)
Pages (from-to)126A
JournalJournal of Investigative Medicine
Volume47
Issue number2
StatePublished - Feb 1999

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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