Cytokine Inhibitors

Carlo Chizzolini and Jean-Michel Dayer, Division of Immunology and Allergy, University Hospital, Geneva, Switzerland

Cytokines deliver information to target cells when the appropriate receptors are expressed at the cell surface. Upon cytokine binding and cytokine-induced receptor aggregation, the signal is transduced resulting in gene activation and/or phenotypic or functional changes of the target cell. Thus, cytokine activity ultimately depends on its concentration in the microenvironment (i.e. in the extracellular fluid or in membrane-bound form) and on the expression level of specific receptors at the surface of responding cells. Cytokine inhibitors may act in several ways and at multiple levels, inhibiting cytokine synthesis and release, modulating the amount of biologically active cytokine in the extracellular milieu, and inhibiting the capacity of the target cell to respond to cytokines (Figure 1). For a better understanding of the field of cytokine inhibitors, it is important to realize that they were discovered as natural products in biological fluids, blocking interleukin-1 or tumor necrosis factor.

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