Pleiotropy and Redundancy Communication between cells in immune and hematopoietic systems is mediated by soluble factors called interleukins or cytokines. These molecules exert their biological functions through specific receptors expressed on the surface of target cells. Most cytokines and their receptors have been identified at the molecular level. Studies with recombinant molecules and their antibodies have revealed that a characteristic feature of cytokines is their functional pleiotropy and redundancy. It was originally thought that each cytokine exerts a specific effect on its particular target cell. However, this is not the case. In fact, most cytokines exhibit a wide range of biological effects on various tissues and cells. Interleukin6 (IL-6) is a typical example of such a multifunctional cytokine (Kishimoto et al., 1992). It was originally identified as a B cell differentiai: ion factor that induces the final maturation of B cells into antibody-producing cells. However, a series of subsequent studies have further revealed that this molecule functions not only in the immune system but also in the hematopoietic, endocrine, hepatic, and even neural systems.

Cytokines also function in a redundant manner; different Icytokines can act on the same cell type to mediate similar effects. For example, not only IL-6 but also IL-2, IL-4, IL-5,, y-interferon (y-IFN), and several other cytokines can iniduce antibody production in B cells. Two pleiotropic cytoikines, leukemiainhibitoryfactor (LIF) and IL-6, wereshown, to act similarly to induce the differentiation of a murine myeloid leukemia cell line (Ml) into macrophages. Although LIF and its receptor are structurally different from IL-6 and its receptor, these two cytokine systems act redundantly not only on Ml cells but also on various tissues and cells. The shared activities of these two cytokines include the following: first, induction of acute phase proteins in hepatocytes; second, induction of maturation of megakaryocytes and platelet formation; third, activation of osteoclasts and bone resorption; and fourth, the promotion of plasmacytoma growth (Hilton and Gough, 1991; Kishimoto et al., 1992). Several other cytokines, including oncostatin M (OM) and IL-1 1, also share some of these