6533b821fe1ef96bd127ae5a
RESEARCH PRODUCT
Effects of leflunomide (HWA 486) on expression of lymphocyte activation markers
H. J. MüllerR. R. BartlettTh. Zielinskisubject
Adultmedicine.medical_specialtyAllergyToluidinesMetaboliteImmunologyHydroxybutyratesTransferrin receptorBiologyPharmacologyLymphocyte ActivationToxicologychemistry.chemical_compoundImmune systemInternal medicineNitrilesReceptors TransferrinmedicineHumansPharmacology (medical)PhytohemagglutininsLeflunomidePharmacologyAniline CompoundsAnti-Inflammatory Agents Non-SteroidalReceptors Interleukin-2Isoxazolesmedicine.diseaseRheumatologyTransplantationchemistryCrotonatesImmunologybiology.proteinAntibodyBiomarkersLeflunomidemedicine.drugdescription
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. Together with previous data, these experiments indicate that leflunomide not only inhibits the expansion of already proliferating lymphocytes, but also impairs PHA and anti-CD3 antibody triggered activation of quiescent cells. Thus, this compound may exert its effects through influencing two important aspects of an immune response, that is, activation and proliferation of lymphocytes.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 1993-06-01 | Agents and Actions |