The molecular regulators of macrophage and granulocyte development. Role of MGI-2/IL-6.

The development of a cell culture system for the in vitro cloning and clonal differentiation of normal hematopoietic cells made it possible to identify the proteins that regulate growth and differentiation of different hematopoietic cell lineages and the change in normal controls that produce leukemia. A model system with myeloid cells has identified different myeloid cell colony-inducing proteins, which we called MGI-1 (= CSF, including IL-3). There is another protein that we first described in 1976 and called MGI-2 in 1980 that induces differentiation of myeloid cells to macrophages or granulocytes without inducing the clonal growth of myeloid cells. The four CSF proteins and IL-1 induce the production of MGI-2 in myeloid cells and MGI-2 induces the production of GM-CSF. This shows the participation of MGI-2 in the network of interactions with different myeloid regulatory proteins. Using a monoclonal antibody to MGI-2, amino acid sequencing, and recombinant protein, we have shown in collaboration with the Genetics Institute that the major form of MGI-2 (MGI-2A) is IL-6. This shows that IL-6 is a myeloid cell differentiation inducing protein. The results also suggest new clinical potentials for MGI-2/IL-6.