Regulation of cytokine gene expression: tumor necrosis factor, interleukin-1, and the emerging biology of cytokine receptors.

Cytokines are bioactive molecules which mediate host responses to inflammatory stimuli. For cytokines to exert their effects, a number of molecular processes must occur. Inflammatory cells must sense the presence of a stimulus, often by detection of that stimulus via cell-surface receptors. Information detected at the cell surface must be transduced intracellularly, and the machinery of cytokine messenger RNA and protein synthesis initiated. Once secreted, cytokines must bind specific receptors on target tissues; these receptors in turn transduce signals which alter target cell phenotypes and responses. Each one of these steps is tightly regulated and may serve as a target for therapeutic manipulation. In this article, the regulation of cytokine gene expression is summarized, with particular emphasis on the regulation of tumor necrosis factor alpha and interleukin-1 biosynthesis. Attention is focused on therapeutic agents which alter cytokine production or activity, some of which are currently used in the ICU.