Effect of inflammatory mediators on the physiology of the human Fallopian tube.

ABSTRACT

The physiological basis for the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of acute pelvic pain in women was examined in terms of (i) the electrophysiological responses of epithelial cells in the human Fallopian tube; and (ii) the longitudinal and circular contractions of the myosalpinx. Epithelial cells were grown as a polarized layer in primary culture, and transepithelial potential difference (p.d.) and short-circuit current (I(scc)) were recorded using a modified Ussing chamber. The inflammatory mediators histamine (0.1-100.0 micromol l(-1)) and platelet activating factor (PAF) (1.9-1900.0 nmol l(-1)) increased p.d. and I(scc) in a dose-dependent manner. Pre-incubation with the NSAID diclofenac sodium (100 micromol l(-1)) inhibited the histamine- and PAF-induced stimulation of p.d. and I(scc). Aspirin (100 micromol l(-1)), ibuprofen (100 micromol l(-1)), indomethacin (100 micromol l(-1)) or naproxen (100 micromol l(-1)) were only partially effective. Histamine (0.1-1000.0 micromol l(-1)) increased the frequency of contractions of longitudinal and circular smooth muscle in segments of Fallopian tube in vitro, in a dose-dependent manner. Pre-incubation with diclofenac significantly reduced the histamine-induced stimulation of tubal smooth muscle contraction at the higher doses of histamine. The other NSAIDs had no effect. These data provide evidence that diclofenac downregulates acute inflammation in the human Fallopian tube and may be of use as an anti-inflammatory agent in the treatment of pelvic inflammatory disease.