0000000000359030
AUTHOR
H. J. Müller
Differential effects of leflunomide on leukocytes: Inhibition of ratin vivo adhesion and humanin vitro oxidative burst without affecting surface marker modulation
Leflunomide has been shown to combat effectively autoimmune diseases in a number of animal models, as well as chronic polyarthritis of humans. Here we report on the effects of this novel drug on the adherence of leukocytes to endothelium, an essential event in establishment and maintenance of inflammation. The entry of cells into tissues is dependent on interactions of adhesion molecules. The process of diapedesis, which these molecules control, involves three phases: tethering, triggering of receptors on endothelial cells and firm attachment of leukocytes to these cells. The interaction of LECAM-1 (constitutively expressed on circulating leukocytes) and P- and E-selectins on the vessel wll…
Effects of leflunomide (HWA 486) on expression of lymphocyte activation markers
Leflunomide (HWA 486), an isoxazol derivative, has been shown to be very effective in combating autoimmune diseases and transplantation rejection in a great number of animal models. The main metabolite of leflunomide, A77 1726, is a potent antiproliferative compound. To further elucidate this effect, lymphocytes of healthy human donors were cultured for 24, 48 or 72 h in the presence of PHA or immobilized anti-CD3 antibody. A77 1726 was added at concentrations between 10 and 100 microM. Flow cytometric evaluation of early activation or proliferation markers (IL-2 and transferrin receptors, respectively) showed that their expression was inhibited in a dose-dependent manner by A77 1726. Toget…
The influence of leflunomide on cell cycle, IL-2-receptor (IL-2-R) and its gene expression
Leflunomide is a novel immunomodulatory drug shown to be very effective in animal models of autoimmune diseases and transplantation rejection, as well as in human rheumatoid arthritis. Leflunomide's main metabolite, A77 1726, has been shown to be reversibly antiproliferativein vitro. Pursuing this, we performed cell cycle analysis by flow cytometry of a B-cell lymphoma line and found that at concentrations >2.5 μM cells accumulated in the early S-phase. In order to determine A77 1726's effects on cell activation, human peripheral blood lymphocytes (PBL) were cultured in the presence of PHA or OKT 3 antibody. Flow cytometric evaluation of IL-2 and transferrin receptor expression exhibited a …