BIOLOGY OF MULTIFUNCTIONAL CYTOKINES - IL-6 AND RELATED MOLECULES (IL-1 AND TNF)

Interleukin 1 (IL 1), IL 6, and tumor necrosis factor (TNF) are typical examples of multifunctional cytokines involved in the regulation of the immune response, hematopoiesis, and inflammation. Their functions are widely overlapping but each shows its own characteristic properties. IL 6 was originally identified as a B cell differentiation factor, and thus one of the major functions of IL 6 is antibody induction. Transgenic mice have provided much needed information on the pathophysiological role of cytokines. With IL 6 transgenic mice, deregulation of the IL 6 expression was suggested to be involved in the generation of plasmacytoma/myeloma and mesangium proliferative glomerulonephritis. The cis-regulatory elements and trans-acting nuclear factor (or factors) for the IL 6 expression (NF-IL 6) have been identified. NF-IL 6 was shown to be a member of a C/EBP family, and the possible involvement of NF-IL 6 not only in the IL 6 regulation but also in the induction of various acute phase proteins was also observed. The findings suggest the presence of a positive regulatory loop in acute-phase reaction. IL 1 receptor belongs to an Ig superfamily, but the IL 6 receptor is a member of a newly identified cytokine receptor family. The IL 6 receptor system was shown to be composed of a ligand binding chain and a signal-transducing molecule. IL 6 was found to trigger the association of these two polypeptide chains. This unique mechanism may be applied to other cytokine receptor systems.