Monokines: stimulatory and inhibitory regulator molecules of myelopoiesis in vitro

The conditions for monocytes to secrete molecules that are involved in myelopoiesis, i.e. Colony Stimulating Factors (CSFs), Interleukin-1 (IL-1) and Tumor Necrosis Factor-alpha (TNF-alpha) were investigated. Whereas secretion of these molecules by monocytes is negligible in a quiescent state, activation of monocytes with Interferon-gamma (IFN-gamma) results in mRNA accumulation and subsequent protein secretion of CSF for granulocytes (G-CSF) and for monocytes (M-CSF). Under identical conditions mRNA-transcripts of TNF-alpha, IL-1-alpha and IL-1-beta genes were induced. Whereas IFN-gamma induces secretion of TNF-alpha protein, protein secretion of IL-1 by monocytes failed to occur in response to an IFN-gamma stimulus. However, the presence in culture of IFN-gamma in combination with TNF-alpha induced secretion of IL-1. Although IL-1 regulates the production of CSF for granulocytes and monocytes (GM-CSF) by IL-1 receptive T-lymphocytes, and is therefore involved in upregulatory mechanisms of myeloid growth, it may be able to suppress growth of myelopoietic progenitor cells (MPC) as well, when hematopoietic cultures are depleted of cells, that have the potential to secrete CSFs. Similarly, IFN-gamma, although being a major inducer of CSF secretion by monocytes, was shown to inhibit myeloid colony growth when exposed to purified MPC and allowed to synergize with TNF-alpha.