Proinflammatory cytokines increase permeability of rat microvascular endothelial cell: Pericyte cocultures in vitro

Abstract

Pericytes (PC) have a unique synergistic relationship with microvascular endothelial cells (MVEC) in the regulation of capillary permeability. This relationship may be important in the increased permeability noted in septic and posttraumatic states. This study investigates the effect of TNF-α, IL-1β, and IL-6 on the permeability of albumin across MVEC:PC coculture barriers. Methods. Semipermeable inserts were coated with gelatin and plated with rat lung MVEC at a concentration of 3 × 10 5 cells/ml. On the fourth day, PCs were added at concentrations to approximate a ratio of 10:1 MVEC:PC. On day 5, 100 ng of TNF-α, IL-1β, and IL-6 were added separately. Following a 24-h incubation period, the clearance of albumin across the coculture barriers was measured. Results. TNF-α and IL-1β significantly increased albumin clearance in comparison to control cocultures ( P < 0.05). IL-6 had no effect on permeability compared to control. Conclusion. TNF-α and IL-1β had a direct effect on MVEC:PC cocultures leading to increased microvascular permeability. Interestingly, IL-6 had no effect, although its presence in high levels has been demonstrated in inflamed lungs. These findings may help elucidate the significance of pericytes in regulating the capillary response to various proinflammatory cytokines.