The ability of the lymphatic system to actively remove fluid from the interstitium is critical to the resolution of
edema. The response of the lymphatics to inflammatory situations is poorly studied, so we examined mesenteric lymphatic contractile activity in the 2,4,6-trinitrobenzenesulfonic
acid (TNBS) model of guinea pig
ileitis, a well-accepted animal model of intestinal
inflammation, by videomicroscopy in vivo and in vitro 1, 3, and 6 days after induction of
ileitis. Lymphatic function (diameter, constriction frequency, amplitude of constrictions, and calculated stroke volume and lymph flow rate) of isolated vessels from TNBS-treated guinea pigs were impaired compared with
sham-treated controls. The dysfunction was well correlated with the degree of
inflammation, with differences reaching significance (P < 0.05) at the highest
inflammation-induced damage observed at day 3. In vivo, significantly fewer lymphatics exhibited spontaneous constrictions in TNBS-treated than
sham-treated animals.
Cyclooxygenase (COX) metabolites were suggested to be involved in this lymphatic dysfunction, since application of nonselective COX inhibitor (10 microM
indomethacin) or a combination of COX-1 and
COX-2 inhibitors (1 microM
SC-560 and 10 microM
celecoxib) markedly increased constriction frequency or induced them in lymphatics from TNBS-treated animals in vivo and in vitro. The present results demonstrate that lymphatic contractile function is altered in TNBS-induced
ileitis and suggest a role for
prostanoids in the lymphatic dysfunction.