scholarly journals The function of the soluble interleukin 6 (IL-6) receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL-6 and prolongation of the plasma half-life of IL-6.

1996 ◽  
Vol 183 (4) ◽  
pp. 1399-1406 ◽  
Author(s):  
M Peters ◽  
S Jacobs ◽  
M Ehlers ◽  
P Vollmer ◽  
J Müllberg ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Acute Phase ◽  
Interleukin 6 ◽  
Acute Phase Response ◽  
Half Life ◽  
Inflammatory Responses ◽  
Phase Response ◽  
Target Cells ◽  
Plasma Half Life

Interleukin 6 (IL-6) is considered an important mediator of acute inflammatory responses. Moreover, IL-6 functions as a differentiation and growth factor of hematopoietic precursor cells, B cells, T cells, keratinocytes, neuronal cells, osteoclasts, and endothelial cells. IL-6 exhibits its action via a receptor complex consisting of a specific IL-6 receptor (IL-6R) and a signal transducing subunit (gp130). Soluble forms of both receptor components are generated by shedding and are found in patients with various diseases such as acquired immune deficiency syndrome, rheumatoid arthritis, and others. The function of the soluble (s)IL-6R in vivo is unknown. Since human (h)IL-6 acts on human and murine target cells, but murine IL-6 on murine cells only, we constructed transgenic mice expressing the hsIL-6R. We report here that in the presence of hsIL-6R, mice are hypersensitized towards hIL-6, mounting an acute phase protein gene induction at significantly lower IL-6 dosages compared to control animals. Furthermore, in hsIL-6R transgenic mice, the detected acute phase response persists for a longer period of time. The IL-6/IL-6R complex prolongs markedly the Il-6 plasma half-life. Our results reinforce the role of the hsIL-6R as an agonistic protein, help to understand the function of the hsIL-6R in vivo, and highlight the significance of the receptor in the induction of the acute phase response.

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.

scholarly journals Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response

2005 ◽  
Vol 102 (19) ◽  
pp. 6843-6848 ◽  
Author(s):  
J. P. Liuzzi ◽  
L. A. Lichten ◽  
S. Rivera ◽  
R. K. Blanchard ◽  
T. B. Aydemir ◽  
...  
Keyword(s):  
Acute Phase ◽  
Interleukin 6 ◽  
Acute Phase Response ◽  
Zinc Transporter ◽  
Phase Response

scholarly journals Acute-phase response factor, a nuclear factor binding to acute-phase response elements, is rapidly activated by interleukin-6 at the posttranslational level

1993 ◽  
Vol 13 (1) ◽  
pp. 276-288
Author(s):  
U M Wegenka ◽  
J Buschmann ◽  
C Lütticken ◽  
P C Heinrich ◽  
F Horn
Keyword(s):  
Transcriptional Regulation ◽  
Acute Phase ◽  
Interleukin 6 ◽  
Acute Phase Response ◽  
Acute Phase Protein ◽  
Phase Response ◽  
Response Factor ◽  
Nuclear Factor ◽  
Response Elements ◽  
Phase Protein

Interleukin-6 (IL-6) is known to be a major mediator of the acute-phase response in liver. We show here that IL-6 triggers the rapid activation of a nuclear factor, termed acute-phase response factor (APRF), both in rat liver in vivo and in human hepatoma (HepG2) cells in vitro. APRF bound to IL-6 response elements in the 5'-flanking regions of various acute-phase protein genes (e.g., the alpha 2-macroglobulin, fibrinogen, and alpha 1-acid glycoprotein genes). These elements contain a characteristic hexanucleotide motif, CTGGGA, known to be required for the IL-6 responsiveness of these genes. Analysis of the binding specificity of APRF revealed that it is different from NF-IL6 and NF-kappa B, transcription factors known to be regulated by cytokines and involved in the transcriptional regulation of acute-phase protein genes. In HepG2 cells, activation of APRF was observed within minutes after stimulation with IL-6 or leukemia-inhibitory factor and did not require ongoing protein synthesis. Therefore, a preexisting inactive form of APRF is activated by a posttranslational mechanism. We present evidence that this activation occurs in the cytoplasm and that a phosphorylation is involved. These results lead to the conclusions that APRF is an immediate target of the IL-6 signalling cascade and is likely to play a central role in the transcriptional regulation of many IL-6-induced genes.

Increased Serum Interleukin-6 Level and Reduction of Hepatic Acute-Phase Response after Major Hepatectomy

1996 ◽  
Vol 28 (2) ◽  
pp. 96-103 ◽  
Author(s):  
F. Kimura ◽  
M. Miyazaki ◽  
T. Suwa ◽  
S. Kakizaki ◽  
H. Itoh ◽  
...  
Keyword(s):  
Acute Phase ◽  
Interleukin 6 ◽  
Acute Phase Response ◽  
Major Hepatectomy ◽  
Phase Response
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