The pivotal role of interleukin 6 in formation and function of hematopoietically active murine long-term bone marrow cultures.

Abstract

The multifunctional cytokine interleukin 6 (IL-6) is involved in the regulation of inflammatory and immune responses, and influences many bone and bone marrow functions. In this report we show high concentrations of IL-6 in the supernatant of murine long-term bone marrow cultures (LTBMC). The concentration increases following medium change peaking 12 h later. IL-6 plays a critical role in the generation and maintenance of myelopoiesis in LTBMC. The addition of monoclonal anti-IL-6 antibody to culture significantly suppresses myeloid cell production. IL-6 is also necessary for stromal layer development and the initiation of myelopoiesis in LTBMC. Horse sera (HS) containing low concentrations of IL-6 did not support LTBMC stromal layer development or myeloid cell production, whereas those with high concentrations did. LTBMC initially set up with horse serum containing high IL-6 concentration produced higher concentrations of colony-stimulating activity and IL-6 at the fifth week after culture initiation than those with low concentrations. The ability of a deficient serum to support myelopoiesis could be improved by the addition of recombinant IL-6 to culture. Similarly, the addition of an anti-IL-6 antibody to culture impaired the ability of a HS to initiate and support myelopoiesis in LTBMC. These results suggest that IL-6 is one of the factors that play an essential role in the formation and function of hematopoietically active LTBMC.