Interleukin 3: from colony-stimulating factor to pluripotent immunoregulatory cytokine

IL-3 is best known as a multicolony-stimulating factor, produced by T-cells, mast cells and eosinophils. Based on its broad spectrum of hemopoietic growth factor activity, the role of IL-3 in the homeostasis of leukocytes is apparent, although the precise mechanisms of this process are yet to be determined. The fact that activated T-helper cells are one of the most potent sources of IL-3 suggests an additional role for IL-3 in the regulation of the immune response. Although the presence of IL-3 receptors on monocytes has been demonstrated, the role of IL-3 in regulating macrophage functions was not clear until recently. We have demonstrated a unique spectrum of macrophage activating properties of IL-3, distinct from that of IFN gamma, IL-4 and other CSFs. These novel macrophage activating properties of IL-3 include its capacity to directly induce the expression of Ia antigens and members of the beta 2 integrin family (e.g. CD11a/CD18[LFA-1]), as well as to contribute to the regulation of cytokine production (IL-1, IL-6 and TNF alpha). Moreover, we observed a significant synergy between IL-3 and IFN gamma in the induction of Ia and LFA-1, as well as between IL-3 and LPS in the induction of Ia and macrophage cytokines. Our data suggest that IL-3 may help control the antigen presentation (AP) capacity of macrophage via the regulation of Ia, beta 2 integrins and macrophage cytokines. It is also possible that the differential state of activation of macrophages that we demonstrated following their induction with IL-3, IFN gamma or IL-3+IFN gamma results in the development of functionally distinct AP cells. Further immunoregulatory properties of IL-3 were observed in vivo by Kimoto and colleagues when IL-3 administration led to profound enhancement of the T-cell-dependent immune response, with no changes in the antibody response to T-cell-independent antigens. Thus, in vitro and in vivo data both confer an immunoregulatory role for IL-3 in the development of the immune response, most likely via its effects on the antigen presenting cells (macrophages). This review will summarize evidence documenting a range of immunoregulatory properties of IL-3 and discuss the mechanisms of action of IL-3.