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The Pivotal Role of Interleukin 6 in Formation and Function of Hematopoietically Active Murine Long-Term Bone Marrow Cultures

Department of Medicine, University of Arkansas for Medical Sciences, and Geriatric Research, Education and Clinical Center (GRECC), John L. McClellan Memorial Veterans Administration Hospital, Little Rock, Arkansas, USA

Key Words. Bone marrow culture • Interleukin 6 • Horse serum • Stroma • Myelopoiesis

Dr. David A. Lipschitz, GRECC (182/LR), John L. McClellan Memorial V.A. Hospital, 4300 West 7th Street, Little Rock, AR 72205, USA.

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.

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