Multifunctional cytokines in haemopoiesis

Abstract

The number of cytokine molecules identified and cloned grows almost weekly. Studies using pure preparations have shown that single entities, e.g. TGFβ and IL-1 act on a wide variety of target cells whereas other cytokines, e.g. G-CSF have a more restricted target cell population. The outcome of stimulation of a cell by a cytokine depends on the target cell type, the presence of other coexisting cytokines and, as the release of cytokines may be targeted in the direction of the stimulus, the orientation of producer and target cells. 1 These modulating phenomena may enable a small number of cytokines to specifically define a much larger number of responses, so that maximum ‘value’ is obtained from the successful evolution of cytokine and receptor molecules. The current nomenclature has little regard for this, the names of cytokines often deriving from the first property observed in vitro. In many cases these are not the most important properties of the molecule and can be misleading, e.g. transforming growth factor β, which is growth inhibitory in some systems; the antiviral action of interferon γ is relatively minor compared to its role as a macrophage activation factor; and interleukin -1 is produced by, and acts on, many cells outside the lymphohaemopoietic system. In addition, although there is often a high degree of homology, the repertoire of activities may vary between species. For example, IL-5 is a growth factor for eosinophils, both in humans and mice, however, in the mouse it also acts as a B-cell differentiation factor—a property which has been less easy to identify in human IL-5. 2 Apart from the ‘haemopoietic growth factors’—IL-3, GM-CSF, G-CSF, M-CSF, IL-5—many of the multifunctional cytokines, e.g. IL-1, IL-2, IL-4, IL-6, TGFβ and TNFα have been shown to be active in the haemopoietic system. In some cases it has not been possible to identify whether these are direct effects on haemopoietic cells or whether they are mediated via the induction of other effector molecules in accessory cell populations. This is currently an area of intensive investigation. This review summarises the properties of these multifunctional cytokines.