Hepatic leukocyte recruitment in response to time-limited expression of TNF-α and IL-1β

The development of chronic liver diseases is mediated by sustained hepatic inflammation. Our objective was to characterize the molecular mechanisms responsible for the hepatic inflammatory response to time-limited TNF-α and IL-1β expression. C57Bl/6 mice were injected with 2 × 107 plaque forming units intraperitoneally of an adenoviral vector containing TNF-α or IL-1β (AdTNF-α or AdIL-1β). A nonreplicating adenoviral vector served as control. Four days later, under ketamine and xylazine anesthesia, the liver microvasculature was examined by intravital microscopy. In the postsinusoidal venules, leukocyte rolling increased significantly in response to both AdTNF-α and AdIL-1β, compared with controls. This response was significantly reduced following injection of an anti-α4-integrin monoclonal antibody (MAb). Postsinusoidal rolling was further reduced to baseline following injection of an anti-P-selectin or anti-L-selectin MAb. Sinusoidal adhesion was greater in mice treated with AdIL-1β than with AdTNF-α. B...