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©2013 UpToDate ® Print Email Mechanisms of action of immunosuppressive drugs Glucocorticoids Inhibits phospholipase A2, cyclooxygenase 2, and nitric oxidesynthetase Inhibits production of pro-inflammatory prostaglandins,leukotrienes, and thromboxanes Inhibits production of IL-1, IL-2, and tumor necrosisfactor-alpha Inhibits neutrophil adhesion to endothelium and chemotaxis Inhibits monocyte/macrophage activation, chemotaxis, andability to recognize antigen Inhibits T lymphocyte proliferative response to antigen Methotrexate Stimulates adenosine release fromfibroblasts and endothelialcells Reduces neutrophil adhesion Antiproliferative effect on synovial fibroblasts andendothelial cells Inhibits leukotriene B4 synthesis by neutrophils Inhibits local IL-1 production Reduces levels of IL-6 and IL-8 Suppresses cell-mediated immunity Inhibits synovial collagenase gene expression Hydroxychloroquine Interferes with normal antigenprocessing Inhibits lysosomal enzymes Inhibits IL-1 release Inhibits polymorphonuclear and lymphocyte responses Sulfasalazine Inhibits polymorphonuclear cellmigration Reduces lymphocyte responses Inhibits angiogenesis Azathioprine Purine analogue; inhibts purinemetabolism Inhibits B- and T-cell lymphocyte functions Inhibits B-cell proliferation and antibody synthesis Inhibits natural killer cell activity Cyclophosphamide andchlorambucil Alkylating agents Crosslinks DNA leading to cell death Produces B- and T-cell lymphocytopenia Inhibits immunoglobulin synthesis Cyclosporine and tacrolimus(FK506) Blocks transcription of IL-2 Suppresses T-cell activation Preferential effect on CD4+ T-lymphocyte Blocks synthesis and release of IL-1 from monocytes Etanercept Neutralizes solubleTNF-alpha, preventing it frombinding to cell bound Infliximab and adalimumab Combine with tumor necrosis factor Down-regulate endothelial cell adhesion molecules Decreases leukocyte migration Leflunomide Inhibits dihydro-orate dehydrogenasewhich leads to depletionof intracellular pyrimidine and reduces RNA synthesis Anakinra IL-1 receptor antagonist