Down-Regulation of the Acute-Phase Response in Patients with Pancreatic Cancer Cachexia Receiving Oral Eicosapentaenoic Acid is Mediated via Suppression of Interleukin-6

1997 ◽  
Vol 92 (2) ◽  
pp. 215-221 ◽  
Author(s):  
Stephen J. Wigmore ◽  
Kenneth C. H. Fearon ◽  
Jean P. Maingay ◽  
James A. Ross
Keyword(s):  
Pancreatic Cancer ◽  
Eicosapentaenoic Acid ◽  
Acute Phase ◽  
Interleukin 6 ◽  
Peripheral Blood ◽  
Acute Phase Response ◽  
Cancer Cachexia ◽  
C Reactive Protein ◽  
Peripheral Blood Mononuclear ◽  
Reactive Protein

1. Weight loss in pancreatic cancer is associated with persistent elevation of the acute-phase protein response. The effect of oral administration of eicosapentaenoic acid on the regulation of the acute-phase response in weight-losing patients with pancreatic cancer was investigated in vitro and in vivo. 2. Oral supplementation with eicosapentaenoic acid, in patients with cancer cachexia, resulted in a significant reduction in the serum concentration of the acute-phase protein C-reactive protein (11.0 ± 4.8 mg/l before eicosapentaenoic acid compared with 0.8 ± 0.8 mg/l after 4 weeks of eicosapentaenoic acid, P < 0.05), but no significant reduction in the serum concentration of the hepatocyte-stimulating cytokine interleukin-6. Production of interleukin-6 by peripheral blood mononuclear cells isolated from patients was significantly reduced after supplementation with eicosapentaenoic acid (interleukin-6 production by peripheral blood mononuclear cells exposed to 10 μg of lipopolysaccharide/ml: 10.2 ± 2.1 ng/ml before supplementation with eicosapentaenoic acid compared with 3.5 ± 1.7 ng/ml after supplementation, P < 0.05) and supernatants from these cells had reduced potential to stimulate C-reactive protein production by isolated human hepatocytes (hepatocyte C-reactive protein production in response to supernatants from peripheral blood mononuclear cell cultures exposed to 10 μg of lipopolysaccharide/ml: 150.4 ± 18.6 ng/ml before eicosapentaenoic acid versus 118 ± 14.9 ng/ml after 4 weeks of eicosapentaenoic acid, P < 0.05). The potential of lipopolysaccharide-stimulated peripheral blood mononuclear cell supernatants to stimulate C-reactive protein production by hepatocytes could be attenuated by neutralizing anti-interleukin-6 antibody in control subjects and in patients before, but not after, treatment with eicosapentaenoic acid. 3. In conclusion, eicosapentaenoic acid can down-regulate the acute-phase response in patients with pancreatic cancer cachexia and this process is likely to involve suppression of interleukin-6 production.

The Effect of Factor Xa/Phospholipid Infusion on the Acute Phase Response in Baboons

1997 ◽  
Vol 77 (02) ◽  
pp. 308-311 ◽  
Author(s):  
Egbert K O Kruithof ◽  
Diane Agay ◽  
Jean Claude Mestries ◽  
Marie-Paule Gascon ◽  
Arnaud Ythier
Keyword(s):  
Acute Phase ◽  
Interleukin 6 ◽  
Acute Phase Response ◽  
Tissue Injury ◽  
Peak Plasma ◽  
Factor Xa ◽  
Phase Response ◽  
C Reactive Protein ◽  
Reactive Protein

SummaryDisseminated intravascular coagulation (DIC) is a frequent complication of septicemia or tissue injury and may be accompanied by elevations of interleukin-6, a mediator of the acute phase response. It is not known whether thrombin or fibrin deposition may directly induce an acute phase response. To study this, we employed a baboon model of in vivo thrombin generation, induced by the administration of purified bovine Factor Xa and phospholipid vesicles. Two Xa/phospholipid dosages were used, a low dosage (2 animals) leading to a rapid 49% decrease in fibrinogen and a high dosage (two injections at 5h interval; 3 animals) leading to complete fibrinogen depletion. Thereafter, fibrinogen levels increased in both treatment groups, reached a maximum of 2.52 ± 0.23 g/1 (mean ± SE, n = 5; p <0.01 with respect to basal levels) at day 2, and returned to normal by day seven. In five control (injection of 0.15% NaCl) baboons no significant changes of fibrinogen were observed (maximal values: 1.88 ± 0.12 g/1). Serum concentrations of C-reactive protein, an acute phase protein, increased from 3.7 ± 0.4 mg/1 to a maximum of 33.0 ± 7.3 at day one, which was five-fold higher (p <0.01) than in control animals at day one (6.2 ± 0.5 mg/1). Transient increases were observed within 6 h for interleukin-6 from basal values of 6.2 ± 1.7 ng/1 to peak plasma levels of 42.9 ±21.4 ng/1, a value threefold higher (p = 0.07) than in control animals (14.8 ± 4.0 ng/1).The preliminary results of this observational study suggest that factor Xa/phospholipid infusion is followed by an acute phase response, leading after one day to significant increases of fibrinogen and of C-reactive protein.

Interleukin-1β stimulates acute phase response and C-reactive protein synthesis by inducing an NFκB- and C/EBPβ-dependent autocrine interleukin-6 loop

2008 ◽  
Vol 45 (9) ◽  
pp. 2678-2689 ◽  
Author(s):  
Frank Kramer ◽  
Jan Torzewski ◽  
Joachim Kamenz ◽  
Kerstin Veit ◽  
Vinzenz Hombach ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Acute Phase ◽  
Interleukin 6 ◽  
Acute Phase Response ◽  
Phase Response ◽  
Interleukin 1Β ◽  
C Reactive Protein ◽  
Reactive Protein

Acute phase response after myocardial infarction: Correlation between serum levels of cytokines and C-reactive protein

1990 ◽  
Vol 68 (21) ◽  
pp. 1083-1083 ◽  
Author(s):  
H. Tilg ◽  
J. Mair ◽  
M. Herold ◽  
W. E. Aulitzky ◽  
P. Lechleitner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Serum Levels ◽  
Phase Response ◽  
C Reactive Protein ◽  
Reactive Protein

The acute phase response and C-reactive protein

2020 ◽  
pp. 2199-2207
Author(s):  
Mark B. Pepys
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Serum Amyloid A ◽  
Acute Phase Proteins ◽  
Phase Response ◽  
Serum Amyloid ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Amyloid A ◽  
Serum Amyloid A Protein

The acute phase response—trauma, tissue necrosis, infection, inflammation, and malignant neoplasia induce a complex series of nonspecific systemic, physiological, and metabolic responses including fever, leucocytosis, catabolism of muscle proteins, greatly increased de novo synthesis and secretion of a number of ‘acute phase’ plasma proteins, and decreased synthesis of albumin, transthyretin, and high- and low-density lipoproteins. The altered plasma protein concentration profile is called the acute phase response. Acute phase proteins—these are mostly synthesized by hepatocytes, in which transcription is controlled by cytokines including interleukin 1, interleukin 6, and tumour necrosis factor. The circulating concentrations of complement proteins and clotting factors increase by up to 50 to 100%; some of the proteinase inhibitors and α‎1-acid glycoprotein can increase three- to fivefold; but C-reactive protein (CRP) and serum amyloid A protein (an apolipoprotein of high-density lipoprotein particles) are unique in that their concentrations can change by more than 1000-fold. C-reactive protein—this consists of five identical, nonglycosylated, noncovalently associated polypeptide subunits. It binds to autologous and extrinsic materials which contain phosphocholine, including bacteria and their products. Ligand-bound CRP activates the classical complement pathway and triggers the inflammatory and opsonizing activities of the complement system, thereby contributing to innate host resistance to pneumococci and probably to recognition and safe ‘scavenging’ of cellular debris. Clinical features—(1) determination of CRP in serum or plasma is the most useful marker of the acute phase response in most inflammatory and tissue damaging conditions. (2) Acute phase proteins may be harmful in some circumstances. Sustained increased production of serum amyloid A protein can lead to the deposition of AA-type, reactive systemic amyloid.

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