Evidence that Tumour Necrosis Factor (TNF) is not Constitutively Present in Vivo The Association of TNF with Freshly Isolated Monocytes Reflects a Rapid in Vitro Production

Tumour necrosis factor (TNF) cytotoxic activity has been shown not to be present in detectable amounts in the serum of healthy humans, but it may be found in some patients with menin-gococcal disease. In this study we investigated whether TNF is constitutively present in vivo on or within monocytes. TNF was detected on freshly isolated paraformaldehyde-fixed monocytes from both healthy individuals and cancer patients. No significant difference was found between the two groups. TNF appeared first 40–60 min after in vitro monocyte adherence, which is the same time as it look TNF to appear extracellularly after the exposure of in vitro cultured monocytes to lipopolysaccharide (LPS). This indicates that TNF associated with freshly isolated monocytes was synthesized in vitro. The inducing signal may be monocyte contact with plastic. Exposure of whole blood to LPS immediately after vein puncture was followed by about twice as rapid TNF release as that observed with in vitro cultured monocytes. The release was inhibited by cycloheximide but not by actinomycin D, indicating that the TNF detected did not represent TNF present in vivo. This is consistent with the fact that no TNF cytotoxic activity was detected in blood cell extracts. However, TNF-mRNA may have been present in vivo. Thus, the available evidence indicates that TNF is not constitutively expressed in vivo.