Tumor Necrosis Factor is secreted by macrophages, monocytes, neutrophils, T cells, natural killer cells following their stimulation by bacterial lipopolysaccharides. Stimulated peripheral neutrophilic granulocytes but also unstimulated cells and also a number of transformed cell lines, astrocytes, microglial cells, smooth muscle cells, and fibroblasts also secrete TNF. Human milk also contains this factor. Cells expressing CD4 secrete TNF-alpha while CD8(+) cells secrete little or no TNF-alpha. The synthesis of TNF-alpha is induced by many different stimuli including interferons, IL-2, GM-CSF, SP, Bradykinin, immune complexes, inhibitors of cyclooxygenase, and PAF (platelet activating factor). Recombinant Human TNF expressed in human 293 cells has been shown to be predominantly a non-covalently linked homotrimer, with a molecular mass of 51 kDa.