Pharmaco-redox regulation of cytokine-related pathways: From receptor signaling to pharmacogenomics

Cytokines represent a multi-diverse family of polypeptide regulators; they are relatively low molecular weight (< 30 kDa), pharmacologically active proteins that are secreted by one cell for the purpose of altering either its own functions (autocrine effect) or those of adjacent cells (paracrine effect). Cytokines are small, nonenzymatic glycoproteins whose actions are both diverse and overlapping (specificity/redundancy) and may affect diverse and overlapping target cell populations. In many instances, individual cytokines have multiple biological activities. Different cytokines can also have the same activity, which provides for functional redundancy (network) within the inflammatory and immune systems. As biological cofactors that are released by specific cells, cytokines have specific effects on cell-cell interaction, communication, and behavior of other cells. As a result, it is infrequent that loss or neutralization of one cytokine will markedly interfere with either of these systems. The biological effect of one cytokine is often modified or augmented by another. Because an interdigitating, redundant network of cytokines is involved in the production of most biological effects, both under physiologic and pathologic conditions, it usually requires more than a single defect in the network to alter drastically the outcome of the process. This fact, therefore, may have crucial significance in the development of therapeutic strategies for biopharmacologic intervention in cytokine-mediated inflammatory processes and infections. (C) 2002 Elsevier Science Inc.