Multiple sclerosis is a complex autoimmune disease of the central nervous system that results in a disruption of the balance between pro-inflammatory and anti-inflammatory signals in the immune system. Given that central nervous system inflammation can be suppressed by various immunological tolerance mechanisms, immune tolerance has become a focus of research in the attempt to induce long-lasti...

The induction of peripheral immune tolerance in the liver is a well-known phenomenon that is operative in different situations, such as tolerance to organ transplants and tolerance to oral antigens. The mechanisms leading to peripheral immune tolerance in the liver are still incompletely understood. While different cell populations of the liver have been implicated in and probably contribute in...

NOD mice develop type 1 autoimmune diabetes and exhibit genetically dominant resistance to transplantation tolerance induction. These two phenotypes are genetically separable. Costimulation blockade fails to prolong skin allograft survival in (NOD x C57BL/6)F1 mice and in NOD-related strains made diabetes-resistant by congenic introduction of protective major histocompatibility complex (MHC) or...

Curing type 1 diabetes by islet transplantation requires overcoming both allorejection and recurrent autoimmunity. This has been achieved with systemic immunosuppression, but tolerance induction would be preferable. Most islet allotransplant tolerance induction protocols have been tested in nonobese diabetic (NOD) mice, and most have failed. Failure has been attributed to the underlying autoimm...

Although transplantation of Vascularized Composite Allografts (VCA) has become a clinical reality, complications resulting from long-term immunosuppression remain major barriers to broader indication. Ideally, induction of tolerance has been considered the Holy Grail in both solid organ and VCA transplantation. Recent advances in immunomodulatory medication and cell-based therapy exploiting don...

midazolam (dormicum) is a benzodiazepine in general anesthesia. midazolam is very suitable for premedication, induction, and maintenance pronounced anxiolytic action, sedation and amnesia, rapid onset of the action, virtually no impairment of cardiovascular or respiratory parameters in therapeutic doses, short duration of action, and excellent local tolerance are among its most important effect...

The mechanistic similarity between acutely and chronically induced morphine tolerance has been previously proposed but remains largely unexplored. Our experiments examined the modulation of acutely induced tolerance to spinally administered morphine by agonists that affect the N-methyl-D-aspartate receptor and nitric oxide synthase systems. Antinociception was detected via the hot water (52.5 d...

Ag-specific tolerance is a highly desired therapy for immune-mediated diseases. Intravenous infusion of protein/peptide Ags linked to syngeneic splenic leukocytes with ethylene carbodiimide (Ag-coupled splenocytes [Ag-SP]) has been demonstrated to be a highly efficient method for inducing peripheral, Ag-specific T cell tolerance for treatment of autoimmune disease. However, little is understood...

Some antigens may induce immunological tolerance not only after injection of high doses (high zone tolerance) but also after injection of subimmunogenic doses (low zone tolerance) (1). Although it is generally agreed that the phenomenon of tolerance results from an effect of antigen on immunocompetent cells, very little is known of the underlying mechanism. In this respect, the phenomenon of lo...