ABSTRACT
BACKGROUND: T cells have a pivotal role in RA. Leflunomide inhibits pyrimidine biosynthesis, to which T cells are especially susceptible, and therefore may have a different cytokine profile than methotrexate. MATERIALS AND METHODS: Serum samples of 100 patients with RA, treated with leflunomide (n = 50) or methotrexate (n = 50), were collected at baseline, after 16 weeks and after 1 year's treatment. Serum levels of interleukin 6 (IL6), and interferon (IFN) gamma were determined by ELISA. Additionally, peripheral blood mononuclear cells (PBMC) of five healthy volunteers and three patients with RA were isolated and the effects of the active metabolite of leflunomide (A77-1726, 0-200 mmol/l) on cell proliferation and on IL6 and IFNgamma production were determined by ELISA. In peripheral blood lymphocytes (PBL) and monocytes (PBM) from two healthy volunteers the effects of A77-1726 on IL6 production were measured by ELISA and PCR. RESULTS: Mean (SEM) serum levels of IFNgamma were significantly reduced after leflunomide treatment (baseline 43 (10) pg/ml; 1 year 29 (7) (p = 0.015), but there was no change in IL6 levels (baseline 158 (41), 1 year 151 (48)). Both IFNgamma and IL6 levels were significantly reduced after methotrexate treatment. This observation was supported by in vitro experiments. The production of IFNgamma by PBL was inhibited by A77-1726, but IL6 production by PBM was not inhibited. CONCLUSION: The differential effect on IFNgamma and IL6 production supports the hypothesis that activated T cells are preferentially inhibited by leflunomide. An explanation may be either inhibition of uridine synthesis or effects on signal transduction pathways.
Subject(s)
Arthritis, Rheumatoid/metabolism , Cytokines/biosynthesis , Immunosuppressive Agents/pharmacology , Isoxazoles/pharmacology , Methotrexate/pharmacology , Adult , Aged , Aniline Compounds/pharmacology , Antirheumatic Agents/pharmacology , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/immunology , Cell Division/drug effects , Cells, Cultured , Crotonates , Dose-Response Relationship, Drug , Double-Blind Method , Follow-Up Studies , Humans , Hydroxybutyrates/pharmacology , Interferon-gamma/biosynthesis , Interleukin-6/biosynthesis , Leflunomide , Middle Aged , Nitriles , ToluidinesABSTRACT
UNLABELLED: The aim of this study was to define the clinical feasibility of planar myocardial 18F-fluorodeoxyglucose (FDG) imaging and to assess the relation between 201Tl, FDG and left ventricular function early after myocardial infarction. METHODS: Fifty-one patients were studied 5 +/- 2 days after infarction. Scintigraphic images were visually and quantitatively analyzed using a circumferential profiles technique. FDG uptake was normalized to the area with maximal 201Tl uptake. Scintigraphic data were compared with left ventricular wall motion as assessed by ventriculography in 22 patients. Relative regional 201Tl uptake was categorized as normal (> or = 75% of peak activity), moderately reduced (50%-75%) or severely reduced (< 50%). These tracer defects were considered viable if FDG uptake exceeded 201Tl uptake by > or = 20% and/or if FDG uptake was normal (> or = 75%). All regions with FDG uptake 20% less than 201Tl uptake were considered nonviable. RESULTS: Four hundred forty-one myocardial regions were analyzed; 200 showed normal 201Tl uptake, 241 had reduced uptake, 191 had moderately reduced 201Tl uptake and 50 regions had severely reduced uptake. Viability for moderately and severely reduced regions was observed in 62% and 48%, respectively. A concordance between flow and metabolism was observed in 38% and 52%, respectively. CONCLUSION: Myocardial FDG imaging is feasible with standard gamma camera systems and enables the identification of regions with preserved glucose metabolism in patients shortly after infarction.
