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

Abstract

SUMMARYSeveral studies have shown that the eytokine interlcukin-6 (IL-6) is produced in response to lumour necrosis faclor (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 afler 2-3 h and levels correlated with Ihe dose of rTNF administered (r = 067, /'=0 004). Peak levels of IL-6 (mean 295, range 266-297 ng//) were lower than those seen in certain disease states despite the very high peak levels of rTNF (mean 11 750, range 5623-1S 620 ng//). These findings suggest that the very high levels of IL-6 found in eerlain disease states are not purely the result of circulating TNF. Other faclors such as cndoloxin or other cytokines may also play a role in determining levels of plasma IL-6.

IL-8 as a circulating cytokine: induction by recombinant tumour necrosis factor-alpha

“…Pre-treatment with indomelhacin had no effect on plasma IL-8 levels, levels at 60 min were essentially the same in untreated (mean 1800 ng//) and indoniethacin-treated subjects (mean 2000 ng//). lL-6 levels in these patients were previously reported [20] essentially, the time course of cytokine production was identical for both lL-8 and lL-6 with both cytokines appearing at 30-60 min and peaking between 2 and 3 h after infusion, There were marked differences in the circulating levels of cytokines; peak levels of 1L-8 {mean peak level 4300 ng//, range 2200 6100) were approximately 17 times higher than those of IL-6 (mean peak level 295 ng. range 266-297) and around three times lower than those of rTNF-a following infusion (mean peak level II 750 ng//, range 5600 18 600. dose 100 /ig/m-.…”

“…GM-CSF, TGF-/(, PDGF or FGF. IL-6 and TNF-a were assayed as described previously using a sandwich ELISA [20]. For the purpose of standardization cytokine levels are quantified in mass terms; these do not necessarily reflect speeific activity which is dependent upon the bioassay system used.…”

Effect of Remifentanil on Mitochondrial Oxygen Consumption of Cultured Human Hepatocytes

“…IL-6 plays an important role in innate and acquired immune responses [50] and is up-regulated during sepsis [51] , [52] . In humans, serum levels of IL-6 are increased after TNF-α infusion [53] , [54] . Opioids can modulate immune responses, and it has been reported previously that remifentanil could prevent endotoxin-induced cytokine release in human whole blood cells in vitro [55] .…”

Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy

“…We focused on TNF in these next studies as opposed to other elevated cytokines be cause of its involvement in a variety of systemic pathological conditions, as well as its pleiotropic effects on other cytokines including IL6 and IFN, which have been shown to be ele vated after IT as well (Boccoli et al, 1990;Blay et al, 1992;Vonderheide et al, 2007). Furthermore, TNF is known to amplify IL6 production (Shalaby et al, 1989;Sheron et al, 1990;Aggarwal, 2003); therefore, we reasoned that TNF inhi bition might account for reductions in other inflammatory Figure 5. Ex vivo LPS-stimulated mouse and human macrophages have increased TNF and IL-6 production in an age-dependent manner.…”