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Infection and Immunity, September 2000, p. 5299-5305, Vol. 68, No. 9
Department of Pediatric Infectious Diseases,
Arkansas Children's Hospital,1 and
Department of Microbiology and
Immunology,2 University of Arkansas for Medical
Sciences, Little Rock, Arkansas, and Department of
Pathology, Sacred Heart Medical Center, Spokane,
Washington3
Received 14 February 2000/Returned for modification 24 March
2000/Accepted 5 June 2000
The role of tumor necrosis factor alpha (TNF-
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Does Inhibition of Tumor Necrosis Factor Alpha Affect Chlamydial
Genital Tract Infection in Mice and Guinea Pigs?
) in host defense
against chlamydial infection remains unclear. In order to further
evaluate the relevance of TNF-
to host resistance in chlamydial
genital tract infection, we examined the effect of local
inhibition of the TNF-
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-
response in guinea pigs infected intravaginally with the guinea
pig strain of Chlamydia psittaci. We successfully blocked the early TNF-
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-
inhibition in mice or guinea
pigs. Analysis of interleukin-1
, macrophage inflammatory protein-2,
and granulocyte macrophage-colony stimulating factor in the mouse model
revealed that blockade of the TNF-
response did not alter the
release of these proinflammatory proteins. Yet, in TNF-
-depleted
mice, increased numbers of neutrophils were detected in the genital
tract, and, in TNF-
-depleted guinea pigs, increased numbers of
neutrophils as well as infiltrating lymphocytes were seen in the
endocervix. Blockade of TNF-
does not affect the level of infection
in mice or guinea pigs, but it may decrease TNF-
-induced apoptosis
of infiltrating inflammatory cells.
*
Corresponding author. Mailing address: Department of
Pediatrics, Department of Microbiology/Immunology, Pediatric Infectious Diseases, Arkansas Children's Hospital, Little Rock, AR 72202. Phone:
(501) 320-1416. Fax: (501) 320-3551. E-mail:
darvilletonil{at}exchange.uams.edu.
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