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Infection and Immunity, September 2000, p. 5299-5305, Vol. 68, No. 9
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?

Toni Darville,1,2,* C. W. Andrews Jr.,3 and R. G. Rank2

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-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.

* 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.

Infection and Immunity, September 2000, p. 5299-5305, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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