Gonococcal infection of human fallopian tube mucosa in organ culture: Relationship of mucosal tissue TNF-alpha concentration to sloughing of ciliatedcells

Background and Objectives: An experimental model consisting of gonococcal i nfection of human fallopian tube mucosa in organ culture has proven useful in studying the molecular pathogenesis of acute gonococcal salpingitis and postsalpingitis sequelae, Gonococcal infection of human fallopian tube muco sa in organ culture results in the sloughing of ciliated epithelial cells f rom the mucosa, This damage to the mucosa can be quantified on fallopian tu be pieces by an assay of the percent of the periphery that has ciliary acti vity (PPCA) remaining at specific time points after infection. Although ass ay of the PPCA has been quite valuable, it is labor-intensive, somewhat sub jective, and requires that the observers have training and experience. A mo re practical assay for genital mucosal damage is desirable for further inve stigations that employ the fallopian tube experimental model. Gonococcal infection of fallopian tube mucosa in organ culture also results in the production of easily quantified tumor necrosis factor-alpha (TNF-al pha) by the mucosa, Furthermore, treatment of the organ cultures with recom binant human TNF-alpha (rHuTNF alpha) alone also causes sloughing of ciliat ed cells from the mucosa, These findings strongly suggest that TNF-alpha is a mediator of the mucosal damage that attends gonococcal infection. Goals of the Study: To determine: (1) whether the PPCA values and the TNF-a lpha concentrations in fallopian tube mucosal tissues correlate closely eno ugh to allow prediction of the PPCA from a measurement of the mucosal tissu e TNF-alpha concentration; and (2) whether the correlation of the TNF-alpha mucosal tissue concentration with the sloughing of ciliated cells (measure d by the PPCA) supports the hypothesis that induction of TNF-alpha by gonoc occal infection, with resultant sloughing of ciliated cells, is likely to b e a major pathogenic mechanism of gonococcal salpingitis and might mediate postsalpingitis infertility and ectopic pregnancy. Study Design: A metaanalysis was performed on studies from three research g roups (two laboratories in the United States and one in the United Kingdom, using identical techniques for quantifying the PPCA, TNF-alpha, or both. Results: There was a close and statistically significant correlation betwee n the TNF-alpha mucosal tissue concentration and the proportion of ciliated cells lost from the mucosa as measured by the PPCA (r = 0,95, p < 0,001), Therefore, as the mucosal tissue concentration of endogenous TNF-alpha incr eased, the loss of ciliated cells from the epithelium increased proportiona tely. Conclusions: During gonococcal infection of human fallopian tube mucosa in organ culture, the mucosal tissue concentration of TNF-alpha can be used to predict the PPCA, and therefore, the extent of mucosal damage. This findin g should facilitate studies of the molecular pathogenesis of infectious dis eases involving human genital mucosa, Further, the close correlation of muc osal TNF-alpha concentration with genital mucosal damage, evaluated by the PPCA, supports the hypothesis that induction of the proinflammatory cytokin e, TNF-alpha, by gonococcal infection, with resultant inflammation and slou ghing of ciliated cells, is an important pathogenic mechanism of gonococcal salpingitis and may mediate postsalpingitis infertility and ectopic pregna ncy as well.