Pharmacological modulation of cytokine action and production through signaling pathways

The action or production of cytokines is mediated through a number of signal transduction pathways which have been elucidated recently. These include pathways integrating the activation of extracellular receptors and subsequent intracellular events leading to alterations of gene expression, cytoskeletal organization, DNA synthesis and cell survival, and the direct activation of intracellular transcription factors via cell permeable hormones. Discovery and characterization of many of these pathways has been aided by the use of compounds which inhibit them. In turn the inhibitors, many of which are already in the clinic, have provided significant insight into the pharmacological importance of each pathway and its potential for providing more potent, selective and safer alternatives. This review summarizes the current state of knowledge about several of these pathways, how they regulate cytokine action or production, and their potential for pharmacological intervention.