Dose-dependent increase in plasma interleukin-6 after recombinant tumour necrosis factor infusion in humans

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Abstract
Several studies have shown that the eytokine interlcukin‐6 (IL‐6) is produced in response to tumour necrosis factor (TNF) in vitro. This study examines the in vivo relation between these two cytokines with assays of plasma IL‐6 and TNF levels in subjects with chronie hepatitis B undergoing immunomoduiatory therapy wilh recombinanl TNF(rTNF). Plasma IL‐6 was detected from 20 min afler rTNF infusion wilh levels peaking after 2–3 h and levels correlated with the dose of rTNF administered (r= 0.67,P=0.004). Peak levels of IL‐6 (mean 295, range 266–297 ng/l) were lower than those seen in certain disease states despite the very high peak levels of rTNF (mean 11 750, range 5623‐18 620 ng/l). These findings suggest that the very high levels of IL‐6 found in certain disease states are not purely the result of circulating TNF. Other factors such as endotoxin or other cytokines may also play a role in determining levels of plasma IL‐6.