INTERLEUKIN-10 STIMULATES HEMATOPOIESIS IN MURINE OSTEOGENIC STROMA

Bone marrow from 5-fluorouracil-treated mice support osteogenesis when cultured in the presence of beta-glycerophosphate and vitamin C. Thes e cultures are unable to support the growth of granulocyte/macrophage colony-forming units for longer than 2 weeks. In contrast, granulocyte /macrophage colony-forming units were detected for more than 6 weeks i n interleukin-10 (IL-10)-treated cultures. In addition, IL-10-treated cultures contain long-term culture initiating cells, suggesting the pr esence of pluripotent hematopoietic cells. Apparently, IL-10 does not directly stimulate the proliferation of granulocyte/macrophage colony- forming units. Interleukin-10 is unable to stimulate [3H]-thymidine in corporation or to increase the number of granulocyte/macrophage colony -forming units in cell suspensions harvested from untreated or interle ukin-10-treated bone marrow cultures. Interleukin-10 acts via an indir ect pathway. Because exogenous transforming growth factor-beta (TGF-be ta) reverses IL-10's stimulatory activity on myeloid progenitors, IL-1 0 most likely works by blocking TGF-beta synthesis, which acts as an e ndogenous suppressor of hematopoiesis in osteogenic marrow cultures. T his is shown further by the increased numbers of granulocyte/macrophag e colony-forming units in cultures treated with neutralizing anti TGF- beta antibodies (1D11.16). Interleukin-10 and 1D11.16 change the cultu red bone marrow stroma from an osteogenic into a hematopoietic morphol ogy. It may be that by blocking endogenous TGF-beta production, IL-10 drives marrow mesenchymal cells away from osteogenic differentiation t oward hematopoietic support.