Cytokines: sources, receptors and signalling.

Cytokines are a family of protein mediators that are important in transducing information between various cell types. These messengers are synthesized by a broad spectrum of cells. Cellular sources of cytokines include those cell types considered to play pivotal roles in the immune system as well as in inflammatory responses, including lymphocytes, monocytes and mast cells. Emerging data indicate that non-immune cells, including epithelial cells and fibroblasts, may also be important sources of certain cytokines. Cytokines fulfill a number of roles during immune and inflammatory reactions, and may display overlapping or redundant functions. In part, this redundancy may arise from the fact that cytokine receptors are not all unique entities, but may be divided into families. Many cytokine receptors have a subunit structure, with common subunits shared between receptors, and serving as affinity modifiers/signal transducers. Cytokines exert their effects on target cells by activating intracellular signalling mechanisms. In addition to 'classical' signal transduction path-ways, new data indicate that cytokines may also exemplify molecules that utilize novel signalling mechanisms, including the Jak-STAT pathways of transcriptional regulation and pathways involving the novel lipid second messenger, ceramide. In conclusion, molecular techniques have enabled the identification of many new cytokines, and the elucidation of their binding sites and mechanisms of action. This information has provided new insights into this complex area. Moreover, an understanding of the molecular basis of cytokine action and the pathways that lead to their acute and chronic effects may, in turn, facilitate interventions to prevent or modify their actions in disease states.