Release of soluble receptors for tumor necrosis factor (TNF) in relation to circulating TNF during experimental endotoxinemia.

Abstract

Serial plasma samples from human volunteers obtained after intravenous administration of Escherichia coli endotoxin were analyzed for the presence of circulating soluble tumor necrosis factor receptors (sTNFR). A four-to fivefold increase of type A (p75) and type B (p55) sTNFR was observed 3 h after endotoxin challenge. Pretreatment of the volunteers with ibuprofen before the injection of endotoxin resulted in a slight increase (3.87±0.2 vs. 3.27±03 ng/ml) and temporal shift of sTNFR-A release concurrent to a marked augmentation of TNF levels (603±118 vs. 338±56 pg/nml) as compared to the group without ibuprofen pretreatment. There was a significant correlation between peak sTNFR-A levels and peak TNF levels in the individual probands (r = 0.52, P = 0.04). On the contrary, release kinetics and plasma concentrations of sTNFR-B were identical in both groups (738±0.69 vs. 7.44±033 ng/ml) and no correlation with individual TNF levels was observed. The amount of sTNFR liberated upon endotoxin challenge was not sufficient to block TNF-mediated cytotoxic effects. Our data indicate that the release in vivo of type A and type B sTNFR upon a short exposure to endotoxin is regulated differently. (J. Clin. Invest. 1992. 90:533-536.)

Circulating soluble tumor necrosis factor receptors, interleukin‐2 receptors, tumor necrosis factor α, and interleukin‐6 levels in rheumatoid arthritis.

“…The expression and shedding of both sTNFR may be distinctly regulated (27,39,40), but the main source of the circulating forms is still unknown. Interestingly, in a recent study, pretreatment with ibuprofen in human experimental endotoxinemia increased and prolonged concentrations of TNFa and p75 sTNFR in the circulation without affecting p55 levels (41). It is therefore possible that concomitant NSAID therapy is also responsible for our findings.…”

Smoking, fat mass and activation of the tumor necrosis factor-α pathway

“…29 Intravenous administration of LPS to healthy volunteers caused a marked increase in sTNFR1 and sTNFR2. 30 The origin of the associations described in this study might be due to direct activation of TNF-a secretion caused by smoking. Repeated exposure to LPS can induce tolerance in target cells.…”

Bacterial-induced release of inflammatory mediators by bronchial epithelial cells

“…Indeed, studies in septic shock patients have demonstrated that the concentrations of circulating TNF-α were raised for several days in these patients and were associated with poor outcome, whilst stable or falling concentrations correlated with survival [15,16]. Similarly, other studies have demonstrated that soluble receptors for TNF-α are also increased in clinical sepsis and experimental E. coli endotoxaemia, and suggest that this may be a natural host defence mechanism, in which the soluble receptors would bind the free circulating TNF-α and thereby prevent or attenuate the biological activity of this cytokine [17,18]. More recently, VAN DEVENTER et al [19] have demonstrated that injection of human volunteers with low doses of E. coli endotoxin led to increased concentrations of IL-8 in the blood, 90 min after injection.…”