Effect of corticosteroids, cyclosporin A, and methotrexate on cytokine release from monocytes and T-cell subsets

Corticosteroids are the most effective drugs in the management of asthma. However, because of their known side effects and the existence of corticosteroid-resistant patients, there is a need for substitute medications in asthma therapy. Using cell lines, in the present study, the two corticosteroids dexamethasone (Dex), and beclomethasone (Bec), as well as the immunosuppressant cyclosporin A (CsA), and the antimetabolic drug methotrexate (Mtx) were examined in their effect on release of immunoreactive IL-1β, IL-2, IL-4, IL-5, and IL-8. THP-1 cells served as a test model for monocytes secreting IL-1β and IL-8 upon stimulation by lipopolysaccharide. Jurkat cells were used as a test model for TH 1-type T-cells and were stimulated for IL-2 release with a combination of phytohemagglutinin and phorbol myristate acetate. Representing TH2-type T-cells, D10.G4.1 cells challenged by anti-CD3-mAb produced IL-4, and IL-5. Considerable qualitative and quantitative differences in the relative efficacy of the test compounds were found. Following IC50 values (nmol/1) of the test compounds were estimated (IL-1β/IL-8/IL-2/IL-4/IL-5): Dex (10.8/35.7/>10,000.0/5.1/4.1), Bec (30.9/102.2/8591.4/0.6/0.4), CsA (318.7/6211.2/2.3/68.2/237.9). Mtx in concentrations up to 10,000.0 nmol/1 was completely inactive. It can be concluded that corticosteroids show another inhibition pattern than CsA: corticosteroids affect mainly Th2-type T-cells, while CsA primarily inhibits the Th1-type T-cell response.)