INTERLEUKIN-12 ENHANCES INTERLEUKIN-3 DEPENDENT MULTILINEAGE HEMATOPOIETIC COLONY FORMATION STIMULATED BY INTERLEUKIN-11 OR STEEL FACTOR

Interleukin 12 (IL-12: natural killer cell stimulatory factor, NKSF; c ytotoxic lymphocyte maturation factor, CLMF) was studied for its effec t on colony formation and lineage expression of low-density bone marro w cells from 5-fluorouracil-treated mice, and of sorted stem cells usi ng a semi-solid culture assay in the absence or presence of IL-3, IL-1 1, Steel factor (SF) and erythropoietin. IL-12 did not support colony formation as a single factor, nor in the presence of IL-11 or SF. In I L-3-containing cultures, IL-12 slightly enhanced neutrophilic and mono cyte differentiation. Both SF and IL-11 synergized with IL-3 to increa se the percentage of multilineage colonies and the number of colonies containing erythrocytes, megakaryocytes, neutrophils, eosinophils, mon ocytes/macrophages, and blast cells, but not mast cells. In the presen ce of IL-3 + IL-11, IL-12 greatly enhanced neutrophil, megakaryocyte, erythrocyte, and mast cell development. In IL-3 + SF-containing cultur es, IL-12 further increased colony numbers and a higher percentage of colonies expressed neutrophilic, megakaryocytic, erythroid, monocytic, blast cell, and/or mast cell lineages. Colony size and the presence o t eosinophils in colonies were unaffected by IL-12 addition. These eff ects of IL-12 could not be reversed by antibodies against interferon-g amma. Our data show that IL-12 may act as a synergistic factor, stimul ating multilineage expression of hemopoietic stem cells, probably via a direct action. The observed activity of IL-1 2, however, required th e presence of at least two factors, i.e. either IL-3 + IL-11, or IL-3 + SF.