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.
Ohteki
T
T
Department of Microbiology, Tohoku University School of Dentistry, Sendai, Japan.
Okamoto
S
S
Nakamura
M
M
Nemoto
E
E
Kumagai
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001172:Arthritis, Rheumatoid; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D017077:Culture Media, Conditioned / Q000737:chemistry; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D018799:Intercellular Adhesion Molecule-1; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008180:Lupus Erythematosus, Systemic; D051379:Mice; D008809:Mice, Inbred C3H / Q000276:immunology; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology*; D008817:Mice, Mutant Strains / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D015850:Interleukin-6; D018799:Intercellular Adhesion Molecule-1