Elevated production of interleukin 6 by hepatic MNC correlates with ICAM-1 expression on the hepatic sinusoidal endothelial cells in autoimmune MRL/lpr mice.

MRL/lpr mice, which are a model of SLE and rheumatoid arthritis in humans, develop profound lymphadenopathy resulting from the accumulation of CD3+ 4-8- double-negative (DN) alpha beta T cells in peripheral lymphoid tissues. We previously indicated that these DN alpha beta T cells preferentially proliferate in the liver and migrate to the periphery. In this study, we analyzed whether any kind of cytokine was produced by hepatic mononuclear cells (MNC) in MRL/lpr mice. The evidence obtained indicates that interleukin 6 (IL-6) was vigorously produced by hepatic MNC in diseased MRL/lpr mice under unstimulated conditions. MNC in the spleen of these mice produced small amounts of IL-6, while those in the lymph nodes did not produce any appreciable amounts of IL-6. These activities of hepatic MNC in diseased MRL/lpr mice were almost completely neutralized by anti-mouse IL-6 monoclonal antibody (mAb). On the other hand, immunohistochemical staining of light- and electron-microscopic analyses revealed that the intracellular cell adhesion molecule 1 (ICAM-1) was expressed on the hepatic sinusoidal endothelial cells of diseased MRL/lpr mice. Moreover, ICAM-1 was newly induced in the hepatic sinusoids of control C3H/He mice by an intravenous injection of 50 units of recombinant mouse IL-6. These data suggest that ICAM-1 expressed on the hepatic sinusoidal endothelial cells in MRL/lpr mice is induced by IL-6, which is produced by hepatic MNC, and that such ICAM-1 may be responsible for the saturation of inflammatory cells and the proliferation of lymphocytes in the liver of MRL/lpr mice.