title: Does inhibition of tumor necrosis factor alpha affect chlamydial genital tract infection in mice and guinea pigs?
abstract: The role of tumor necrosis factor alpha (TNF-alpha) in host defense against chlamydial infection remains unclear. In order to further evaluate the relevance of TNF-alpha to host resistance in chlamydial genital tract infection, we examined the effect of local inhibition of the TNF-alpha response in normal C57 mice and in interferon gamma gene-deficient C57 mice infected intravaginally with the mouse pneumonitis agent of Chlamydia trachomatis. Since the guinea pig model of female genital tract infection more closely approximates the human in terms of ascending infection and development of pathology, we also examined the effect of local inhibition of the TNF-alpha response in guinea pigs infected intravaginally with the guinea pig strain of Chlamydia psittaci. We successfully blocked the early TNF-alpha response in the respective animal models. This blockade had no effect on the numbers of organisms isolated from the genital tract during the time of TNF-alpha inhibition in mice or guinea pigs. Analysis of interleukin-1beta, macrophage inflammatory protein-2, and granulocyte macrophage-colony stimulating factor in the mouse model revealed that blockade of the TNF-alpha response did not alter the release of these proinflammatory proteins. Yet, in TNF-alpha-depleted mice, increased numbers of neutrophils were detected in the genital tract, and, in TNF-alpha-depleted guinea pigs, increased numbers of neutrophils as well as infiltrating lymphocytes were seen in the endocervix. Blockade of TNF-alpha does not affect the level of infection in mice or guinea pigs, but it may decrease TNF-alpha-induced apoptosis of infiltrating inflammatory cells.
authors.affiliation: Department of Pediatric Infectious Diseases, Arkansas Children's Hospital, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72202, USA. darvilletonil@exchange.uams.edu
authors.forename: T
authors.initials: T
authors.lastname: Darville
authors.forename: C W
authors.initials: CW
authors.lastname: Andrews
authors.forename: R G
authors.initials: RG
authors.lastname: Rank
mesh_terms: D000818:Animals; D002690:Chlamydia Infections / Q000209:etiology* / Q000473:pathology; D005260:Female; D005831:Genital Diseases, Female / Q000209:etiology* / Q000473:pathology; D007371:Interferon-gamma / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma