Modulation of leukocyte-endothelial cell interactions and microvascular dysfunction by endogenous interleukin-10

The objective of this study was to determine whether endogenous IL-10 is capable of regulating leukocyte recruitment under baseline conditions and in response to inflammatory stimuli. Intravital microscopy was used to examine leukocyte rolling and adhesion in cremasteric postcapillary venules in wild-type mice and in 10 wk old IL-10^-/- mice. Under baseline conditions, leukocyte rolling was elevated in IL-10^-/- mice, but IL-10^-/- and wild-type mice responded similarly to the acute chemotactic stimulus, fMLP. In response to LPS (30 μg/kg, i.v.), leukocyte rolling and adhesion and FITC-albumin extravasation were greatly enhanced in the IL-10^-/- mice. In addition, leukocyte recruitment into the lung, determined by myeloperoxidase assay, was higher in IL-10^-/- mice. A further increase in leukocyte rolling and an enhanced response to fMLP was observed in 15 wk old IL-10^-/- mice. These results suggest that endogenous IL-10 may modulate leukocyte rolling and adhesion and microvascular dysfunction in response to inflammatory stimuli. In addition this regulatory role may become more important over time.