Tumor necrosis factor (TNF)-alpha but not TNF-beta induces secretion of colony stimulating factor for macrophages...

Tumor necrosis factor (TNF)-alpha has been identified as a major inducer of colony stimulating factor (CSF)-secretion by human vascular endothelial cells and fibroblasts. In the present study we assessed the capacity of TNFs to induce release of CSF-1 from highly purified peripheral blood monocyte preparations. Whereas monocytes do not accumulate CSF-1 messenger (m)RNA constitutively and consequently do not produce CSF-1 protein, CSF-1 mRNA and protein secretion became detectable, when monocytes were cultured in the presence of TNF-alpha, that was synergistically enhanced by interferon-gamma (IFN-gamma). However, under identical experimental conditions TNF-beta failed to induce monocyte CSF-1 synthesis. Cultures of monocytes in the presence of TNF-beta before addition of TNF-alpha abolished the CSF-1 inducing capacity of TNF-alpha, suggesting that TNF-beta may act as antagonist to TNF-alpha for CSF-1 production. These data point out a previously unrecognized function of TNF-alpha to modulate CSF-1 release by monocytes and demonstrate disparate biological properties of different TNF species in hematopoiesis.