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

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.