Does inhibition of tumor necrosis factor alpha affect chlamydial genital tract infection in mice and guinea pigs?

The role of tumor necrosis factor alpha (TNF-alpha) in host defense against chlamydial infection remains unclear. In order to further evaluate the rel evance of TNF-alpha to host resistance in chlamydial genital tract infectio n, 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 in travaginally with the mouse pneumonitis agent of Chlamydia trachomatis. Sin ce the guinea pip model of female genital tract infection more closely appr oximates the human in terms of ascending infection and development of patho logy, we also examined the effect of local inhibition of the TNF-alpha resp onse in guinea pigs infected intravaginally with the guinea pig strain of C hlamydia 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 inh ibition in mice or guinea pigs. Analysis of interleukin-1 beta, macrophage inflammatory protein-2, and granulocyte macrophage-colony stimulating facto r in the mouse model revealed that blockade of the TNF-alpha response did n ot alter the release of these proinflammatory proteins. Yet, in TNF-alpha-d epleted mice, increased numbers of neutrophils were detected in the genital tract, and, in TNF-alpha-depleted guinea pigs, increased numbers of neutro phils as well as infiltrating lymphocytes were seen in the endocervix. Bloc kade 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 infla mmatory cells.