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|Parts of this cytokine network were found to
function not only within the hematopoietic cell system but also in some
nonhematopoietic cell types. Endothelial cells that make blood
vessels produce IL-6 at the time of new blood vessel formation (angiogenesis), and the production of IL-6 is switched off when angiogenesis has been completed (51). The transient expression of IL-6 in the endothelial cells indicates a role for IL-6 in angiogenesis in addition to its role in regulating the development of myeloid and lymphoid hematopoietic cells. IL-6 can also induce the production of acute phase proteins in liver cells (22). The pleiotropic effects of a cytokine such as IL-6 raise the question whether these effects on different cell types are direct or are indirectly mediated by IL-6 switching on production of
other regulators that vary in the different cell types. Interpretation of experimental data on the effect of each cytokine therefore has to take into account that the cytokine functions
in a network of interactions, so as to avoid an incorrect assignment of a specific effect to a direct action of a particular cytokine. This network has also to be taken into account in the
clinical use of these cytokines. What can be therapeutically useful may be due to the direct action of an injected cytokine or to an indirect effect due to other cytokines that are switched on in vivo.
A network of interactions allows considerable flexibility depending on which part of the network is activated. It also allows ready amplification of response to a particular stimulus
such as bacterial lipopolysaccharide (reviewed in ref. 27). In addition to the flexibility of this network both for the response to present-day infections and to different types of infections
that may develop in the future, a network may also be necessary to stabilize the whole system.