Inhibition of monocyte/endothelial cell interactions and monocyte adhesion molecule expression by the immunosuppressant mycophenolate mofetil.

Study Design: In vitro study on the effects of mycophenolate mofetil (MMF) on isolated human monocytes and endothelial cells.

Objectives: Haematogenous macrophages play an essential role in the development of secondary damage following spinal cord injury (SCI), and there is evidence that the use of immunosuppressants such as MMF can reduce monocyte invasion and neuronal damage.

Setting: University Hospital for Orthopaedic Surgery, Frankfurt am Main, Germany.

Astrocytic factors down-regulate the expression of major histocompatibility complex-class-II and intercellular adhesion molecule-1 on human monocytes.

Several factors contribute to the maintenance of central nervous system immune privilege and astrocytes have been identified as a major source of immunomodulatory cytokines. To investigate whether hematogenous monocytes are immunologically deactivated by astrocyte-derived factors human monocytes were stimulated with lipopolysaccharide or interferon (IFN)-gamma and treated with the supernatant from pure astrocyte cultures, interleukin (IL)-4, IL-10, or with IL-1-receptor antagonist (1L-1-RA). Flow cytometry demonstrated that the supernatant from astrocyte cultures was the most potent agent in reducing the levels of major histocompatibility complex (MHC)-class-II- as well as intercellular adhesion molecule-1-expression, whereas IL-4, IL-10, and IL-1-RA had only marginal effects.