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

Toshiaki Ohteki, Shigefumi Okamoto, Masanori Nakamura, Eiji Nemoto, Katsuo Kumagai

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21 Citations (Scopus)

Abstract

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) αβT cells in peripheral lymphoid tissues. We previously indicated that these DN αβT 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.

Original languageEnglish
Pages (from-to)145-152
Number of pages8
JournalImmunology Letters
Volume36
Issue number2
DOIs
Publication statusPublished - 1993 May

Keywords

  • Hepatic MNC
  • Hepatic sinusoidal endothelial cell
  • ICAM-1
  • Interleukin 6
  • MRL/lpr mouse

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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