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Tumor necrosis factor-α (TNF-α) has been implicated as a key mediator in the progression of rheumatoid arthritis. Inhibitors of phosphodiesterase IV (PDE IV) have been shown to inhibit the production of TNF-α by elevating intracellular levels of cyclic adenosine monophosphate (cAMP). Our efforts in a series of biarylcarboxamides have led to the identification of 8j (CP-353,164) as a potent inhibitor...
Subcutaneous administration of Granulocyte-macrophage-colony stimulating factor (GM-CSF) to mice enhanced LPS-induced cytokine production in the circulation (TNF, IL-6) and peritoneal cavity (IL-1β, IL-6). This effect was induced rapidly (within 1 h) and persisted for 4 h. Mice made leukopenic with cyclophosphamide retained the ability to respond to GM-CSF. In addition, TNF induced IL-6 production...
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