Daily production of human tumor necrosis factor in LPS-stimulated ex vivo blood culture assays

Tumor necrosis factor (TNF) is a pleiotropic cytokine with immunological an d neuroendocrine activities, A useful tool for studying TNF is the measurem ent of its in vitro and/or ex vivo over-expression, induced by a variety of stimuli on isolated peripheral mononuclear cells or whole blood, respectiv ely. The capacity to over-express TNF, in ex vivo LPS-stimulated whole bloo d from 18 normal individuals, showed inter-individual variations ranging fr om high (3 ng/ml) to low (0.7 ng/ml) producers. Although at a lower level, a similar situation was observed in the spontaneous production of the cytok ine, In order to detect cyclic effects in these variations, blood samples w ere taken at 08:00, 12:00, 16:00 and 20:00 hours, from nine healthy volunte ers, and cultured in the ex vivo system. TNF and cortisol were measured by immunometric assays. Both, LPS-stimulated whole blood and plasma showed imp ortant, individual variations in TNF levels. Although cortisol levels prese nted a normal circadian cycle, these individual patterns in TNF production were basically conserved during the day (p > 0,05), and no correlation was observed between the levels of the hormone and those of the cytokine, When total TNF levels were determined at 20:00 hours, a moderate, temporary vari ation pattern of the cytokine production was found. These results suggest t hat cortisol does not play a predominant role in determining the ex vivo ca pacity of blood to produce TNF. Presumably, the variable capacity to produc e the cytokine may have a strong genetic component.