Background. Transmigration of neutrophils (PMNs) through endothelial c
ell tight junctions is a critical stage in the tissue injury of ischem
ia-reperfusion (I/R). Although cytokines are released in I/R, it is un
clear whether cytokines directly increase permeability or this phenome
non requires both expression of cell adhesion molecules and PMN adhesi
on-activation. Methods. We exposed confluent monolayers of human umbil
ical vein endothelial cells to physiologic concentrations of interleuk
in-1 (10 pg/ml) and tumor necrosis factor-alpha (10 pg/ml) in the abse
nce of PMNs. Tight junction permeability was quantified with both tran
sendothelial electrical resistance and albumin flux, whereas expressio
n of endothelial-leukocyte adhesion molecule-1 was measured by flow cy
tometry (t test p < 0.05). Results. Simulation with tumor necrosis fac
tor-alpha or interleukin-1 produced maximal transendothelial electrica
l resistance decreases at 12 hours with return to baseline at 24 hours
. Increases in albumin flux began at 6 hours, with maximum effects at
24 hours. These changes occurred soon after maximal expression of endo
thelial-leukocyte adhesion molecular-1 at 4 hours. Conclusions. Cytoki
nes induced increased in both cell adhesion molecule expression and en
dothelial permeability. This sequence of events is consistent with dir
ect cytokine effects on cytoarchitecture, because is occurred without
the adhesion-activation of PMNs.