The Acute-phase Response Is Not Predictive for the Development of Arthritis in Seropositive Arthralgia – A Prospective Cohort Study

2012 ◽  
Vol 39 (10) ◽  
pp. 1914-1917 ◽  
Author(s):  
MAARTEN LIMPER ◽  
LOTTE van de STADT ◽  
WOUTER BOS ◽  
MARTIJN de KRUIF ◽  
ARNOLD SPEK ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Messenger Rna ◽  
Immunoglobulin M ◽  
Phase Response ◽  
Low Grade ◽  
Baseline Serum ◽  
Tnf Α ◽  
Clinical Arthritis

Objective.To evaluate whether markers of the acute-phase response in patients presenting with arthralgia and positive anticitrullinated protein antibodies (ACPA) and/or immunoglobulin M rheumatoid factor (IgM-RF) could be predictive for the development of arthritis.Methods.In total, 137 ACPA- and/or IgM-RF-positive patients were included. Patients were followed annually for the development of arthritis, defined as presence of 1 or more swollen joints at clinical examination. High-sensitivity C-reactive protein (hsCRP), procalcitonin (PCT), secretory phospholipase A2 (SPLA2), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), IL-12p70, IL-10, and interferon-γ (IFN-γ) were measured in baseline serum samples. Gene expression focusing on a predefined panel of genes coding for inflammatory molecules was measured by multiplex ligation-dependent probe amplification.Results.Thirty-five patients (26%) developed arthritis within a median time of 11 months (interquartile range 3.7–18 mo). Circulating levels of cytokines, SPLA2, hsCRP, and PCT were not different between patients with progression to clinical arthritis and those without progression. However, a trend for IL-12p70, TNF-α, IL-10, IL-6, and SPLA2 was observed. No correlation between messenger RNA (mRNA) expression levels of inflammatory genes and progression to arthritis was found. Subgroup analysis of patients with early progression to arthritis showed higher levels of mRNA expression of poly(A)-specific ribonuclease and polycomb complex protein BMI-1 compared to patients without progression to arthritis.Conclusion.Although low-grade inflammation is present before onset of clinical arthritis in large cohorts and can be detected using consecutive measurements, a single measurement of acute-phase reactants seems to have limited value for prediction of development of arthritis in individual patients.

Immune Alterations, Lipid Peroxidation, and Muscle Damage Following a Hill Race

2005 ◽  
Vol 30 (2) ◽  
pp. 196-211 ◽  
Author(s):  
Richard J. Simpson ◽  
Martin R. Wilson ◽  
James R. Black ◽  
James A. Ross ◽  
Greg P. Whyte ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Muscle Damage ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Venous Blood ◽  
Total Antioxidant Status ◽  
Phase Response ◽  
Tnf Α

Hill races usually include large downhill running sections, which can induce significant degrees of muscle damage in a field setting. This study examined the link between muscle damage, oxidative stress, and immune perturbations following a 7-km mountainous hill race with 457 m of ascent and 457 m of descent. Venous blood samples were taken from 7 club level runners before, immediately after, and 48 hrs postrace. Samples were analysed for total and differential leukocyte counts, markers of muscle damage (CK), lipid peroxidation (MDA), and acute phase proteins (CRP; fibrinogen; α-1-ACT). The total antioxidant status (TEAC) and plasma levels of the proinflammatory cytokines IL-6, IL-8, and TNF-α were also determined. Subjective pain reports, and plasma activities of CK, MDA, and circulatory monocytes reached peak values at 48 hrs postrace (p <  0.05). TEAC and the cytokine IL-8 increased immediately after the race (p <  0.05). Plasma TNF-α remained unchanged (p > 0.05). Despite the reports of muscle damage and soreness, no evidence of an acute phase response was observed (p > 0.05), which may be explained by the failure of the race to induce a plasma TNF-α response. Future studies should examine the link between muscle damage, oxidative stress, and the acute phase response following hill races of longer duration with larger eccentric components. Key words: acute phase response, cytokines, antioxidant capacity, creatine kinase, field study

Follistatin concentrations in male sheep increase following sham castration/castration or injection of interleukin-1β

1996 ◽  
Vol 151 (1) ◽  
pp. 119-124 ◽  
Author(s):  
D J Phillips ◽  
M P Hedger ◽  
J R McFarlane ◽  
R Klein ◽  
I J Clarke ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Interleukin 2 ◽  
Inhibitory Effect ◽  
Phase Response ◽  
Interleukin 1Β ◽  
Tnf Α ◽  
Recombinant Interleukin 2 ◽  
Factor Α ◽  
Male Sheep

Abstract Plasma follistatin (FS) concentrations were determined after castration (n=5) or sham castration (n=4) of mature rams. Both treatments resulted in a prolonged increase in FS between 7 and 19 h after surgery, which returned to pretreatment concentrations by 24 h. Tumour necrosis factor-α (TNF-α), a sensitive marker of an acute-phase response, was undetectable in plasma, indicating that the FS response was not induced by trauma due to surgery. In a second experiment, injection of castrated rams (n=4) with ovine recombinant interleukin-1β, an acute-phase mediator, resulted in a sustained rise in FS concentrations within 4 h of injection. Plasma TNF-α concentrations increased transiently within 1 h of interleukin-1β injection, indicating that an acute-phase response had been initiated. Plasma follicle-stimulating hormone (FSH) concentrations were significantly decreased at 8 and 24 h after interleukin-1β injection, strongly suggestive of an inhibitory effect of increased FS concentrations on the secretion of FSH. Injection of castrated rams (n=2) with a control preparation of recombinant interleukin-2 did not induce an acute-phase response, and plasma FS and FSH concentrations were unaffected. These data show that the testis is not a major source of circulating FS, that the increase in circulating FS following sham castration/castration is not due to an acute-phase response, but that conversely FS concentrations are modulated by the acute-phase mediator, interleukin-1β. Journal of Endocrinology (1996) 151, 119–124

Strong relationships between mediators of the acute phase response and fatty liver in dairy cows

2005 ◽  
Vol 85 (2) ◽  
pp. 165-175 ◽  
Author(s):  
B. N. Ametaj ◽  
B. J. Bradford ◽  
G. Bobe ◽  
R. A. Nafikov ◽  
Y. Lu ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Dairy Cows ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Phase Response ◽  
Prostaglandin E ◽  
Total Lipids ◽  
Amyloid A ◽  
Tnf Α ◽  
Strong Relationships

The objective of this study was to investigate the relationship between activation of acute phase response and fatty liver in transition dairy cows. Fatty liver was induced in dairy cows by feeding 8 kg of cracked corn 1 mo before the expected day of parturition. Liver and blood samples were obtained at days -4, 3, 8, 12, 14, 22, 27, and 36 postpartum. Cows that developed fatty liver (n = 4) reached peak total lipids in the liver at day 12 postpartum with 11.4% (wet wt.) compared with 6.6% in control cows (n = 4). Cows with fatty liver had greater plasma tumor necrosis factor-alpha (TNF-α), nonesterified fatty acids (NEFA), and lower lactate concentrations than did control cows at day -4. During highest concentrations of total lipids in the liver, for at least one time-point, fatty-liver cows had greater concentrations of plasma serum amyloid A (SAA), haptoglobin, and NEFA and lower concentrations of calcitonin gene-related peptide (CGRP), prostaglandin E2 (PGE2), cortisol, and TNF-α than did control cows. Concentrations of total lipids in the liver at 12 d postpartum were correlated (a) positively with plasma TNF-α, SAA, and NEFA and negatively with plasma CGRP before calving, (b) positively with plasma SAA, haptoglobin, and NEFA and negatively with plasma PGE2, CGRP, total cholesterol, and glucose at days 3, 8, and 12 postpartum, and (c) negatively with concentrations of plasma glucose, lactate, and total bilirubin after day 12 postpartum. In conclusion, this study indicates that the acute phase response occurs in cows with fatty liver as well as strong relationships between mediators of immune response and fatty liver. Key words: Acute phase response, fatty liver, dairy cow

In vivo regulation of plasma platelet-activating factor acetylhydrolase during the acute phase response

1999 ◽  
Vol 277 (1) ◽  
pp. R94-R103 ◽  
Author(s):  
Riaz A. Memon ◽  
John Fuller ◽  
Arthur H. Moser ◽  
Kenneth R. Feingold ◽  
Carl Grunfeld
Keyword(s):  
Mrna Expression ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Platelet Activating Factor ◽  
Phase Response ◽  
Mrna Levels ◽  
Potent Inducer ◽  
Platelet Activating Factor Acetylhydrolase ◽  
Infection And Inflammation ◽  
Lps Treatment

Plasma platelet-activating factor acetylhydrolase (PAF-AH) hydrolyzes PAF and oxidized phospholipids and is associated with lipoproteins in the circulation. Endotoxin [lipopolysaccharide (LPS)], a potent inducer of the acute phase response (APR), produces marked changes in several proteins that play important roles in lipoprotein metabolism. We now demonstrate that LPS produces a 2.5- to 3-fold increase in plasma PAF-AH activity in Syrian hamsters. The plasma PAF-AH activity is found in the high-density lipoprotein (HDL) fraction and is increased threefold with LPS treatment despite a decrease in plasma HDL levels, indicating that plasma PAF-AH activity is increased per HDL particle. LPS markedly increased PAF-AH mRNA levels in liver, spleen, lung, and small intestine. The maximal increase in plasma PAF-AH activity and mRNA expression in liver and spleen is seen 24 h after LPS treatment. Both tumor necrosis factor and interleukin-1 modestly increased plasma PAF-AH activity and mRNA levels in liver and spleen, suggesting that they may partly mediate the effect of LPS on PAF-AH. Surgical removal of spleen had no effect on basal or LPS-induced plasma PAF-AH activity, suggesting that spleen per se may not contribute to plasma PAF-AH activity. Finally, LPS, turpentine and zymosan increased plasma PAF-AH activity in mice and/or rats, indicating that multiple APR inducers upregulate plasma PAF-AH and this effect is consistent across different rodent species. Taken together, our results indicate that plasma PAF-AH activity and mRNA expression is markedly upregulated during the host response to infection and inflammation. An increase in plasma PAF-AH may enhance the degradation of PAF as well as alter the structure and function of HDL during infection and inflammation.

scholarly journals The influence of glucocorticoid on the fibrinogen messenger RNA content of rat liver in vivo and in hepatocyte suspension culture

1984 ◽  
Vol 220 (3) ◽  
pp. 631-637 ◽  
Author(s):  
H M G Princen ◽  
H J Moshage ◽  
H J W de Haard ◽  
P J van Gemert ◽  
S H Yap
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Messenger Rna ◽  
Acute Phase Proteins ◽  
Rat Hepatocytes ◽  
Phase Response ◽  
Control Value ◽  
Hepatocyte Suspension

The plasma concentration of fibrinogen, one of the major acute-phase proteins produced by the liver, increases during the acute-phase response as a result of enhanced synthesis in liver. Since adrenal-cortical hormones have been thought to have a key role in the regulation of the fibrinogen synthesis, fibrinogen-polypeptide mRNA sequences were determined in the present study, by using a specific complementary-DNA probe, in RNA fractions obtained from rat hepatocytes exposed to glucocorticoids in vitro (hepatocyte suspension cultures) and in vivo. Maximal induction of the fibrinogen-polypeptide mRNA (to 400% of the control value) was found in vitro at 0.1 microM-dexamethasone after 9 h of incubation. The same magnitude of induction was obtained with 20 microM-cortisol or 60 microM-corticosterone. In contrast with the findings in vitro, no induction of the fibrinogen-polypeptide mRNA was observed in the liver at various times after injection of different doses of glucocorticoids into rats. These results suggest that more complex regulatory mechanisms are involved and that glucocorticoids are not the sole regulatory factors in vivo in the enhanced synthesis of fibrinogen during the acute-phase response.

scholarly journals Ageing Is Associated with a Prolonged Fever Response in Human Endotoxemia

2001 ◽  
Vol 8 (2) ◽  
pp. 333-338 ◽  
Author(s):  
Karen Suárez Krabbe ◽  
Helle Bruunsgaard ◽  
Christian Muff Hansen ◽  
Kirsten Møller ◽  
Lise Fonsmark ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
The Elderly ◽  
Young Group ◽  
Elderly Group ◽  
Phase Response ◽  
Endotoxin Administration ◽  
Prolonged Fever ◽  
Tnf Α ◽  
Fever Response

ABSTRACT The purpose of this study was to investigate whether an age-associated impaired acute-phase response exists. Nine healthy elderly volunteers (median, 66 years; range, 61 to 69 years) and eight young controls (median, 24 years; range, 20 to 27 years) were given an intravenous bolus of endotoxin (2 ng/kg). The rectal temperature was monitored continuously, and blood samples for cytokine measurements were obtained before endotoxin administration as well as 0.5, 1, 1.5, 2, 3, 4, 8, 12, and 24 h after the injection. The elderly subjects showed a more prolonged fever response compared to the young controls. Levels of tumor necrosis factor alpha (TNF-α), soluble TNF receptors (sTNFR-I), interleukin-6 (IL-6), IL-8, IL-10, and IL-1 receptor antagonist (IL-1ra) in plasma increased markedly following endotoxin administration in both groups. The elderly group showed larger initial increases in TNF-α and sTNFR-I levels and prolonged increased levels of sTNFR-I. Monocyte concentrations decreased in both groups, with the elderly group showing a more rapid decrease and a slower subsequent increase than did the young group. Furthermore, the elderly group had a more rapid increase in C-reactive protein levels than did the young group. In conclusion, ageing is associated with an altered acute-phase response including initial hyperreactivity, prolonged inflammatory activity, and prolonged fever response.

scholarly journals The Acute Phase Response Is a Prominent Renal Proteome Change in Sepsis in Mice

2019 ◽  
Vol 21 (1) ◽  
pp. 200 ◽  
Author(s):  
Beáta Róka ◽  
Pál Tod ◽  
Tamás Kaucsár ◽  
Matej Vizovišek ◽  
Robert Vidmar ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Mrna Expression ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Acute Phase Proteins ◽  
Late Phase ◽  
Kidney Injury ◽  
Phase Response ◽  
Complement C3 ◽  
Saline Control

(1) Background: Sepsis-induced acute kidney injury (AKI) is the most common form of acute kidney injury (AKI). We studied the temporal profile of the sepsis-induced renal proteome changes. (2) Methods: Male mice were injected intraperitoneally with bacterial lipopolysaccharide (LPS) or saline (control). Renal proteome was studied by LC-MS/MS (ProteomeXchange: PXD014664) at the early phase (EP, 1.5 and 6 h after 40 mg/kg LPS) and the late phase (LP, 24 and 48 h after 10 mg/kg LPS) of LPS-induced AKI. Renal mRNA expression of acute phase proteins (APP) was assessed by qPCR. (3) Results: Renal proteome change was milder in EP vs. LP. APPs dominated the proteome in LP (proteins upregulated at least 4-fold (APPs/all): EP, 1.5 h: 0/10, 6 h: 1/10; LP, 24 h: 22/47, 48 h: 17/44). Lipocalin-2, complement C3, fibrinogen, haptoglobin and hemopexin were the most upregulated APPs. Renal mRNA expression preceded the APP changes with peak effects at 24 h, and indicated renal production of the majority of APPs. (4) Conclusions: Gene expression analysis revealed local production of APPs that commenced a few hours post injection and peaked at 24 h. This is the first demonstration of a massive, complex and coordinated acute phase response of the kidney involving several proteins not identified previously.

Regulation of urea synthesis during the acute-phase response in rats

2013 ◽  
Vol 304 (7) ◽  
pp. G680-G686 ◽  
Author(s):  
Karen Louise Thomsen ◽  
Niels Jessen ◽  
Andreas Buch Møller ◽  
Niels Kristian Aagaard ◽  
Henning Grønbæk ◽  
...  
Keyword(s):  
Acute Phase ◽  
Acute Phase Response ◽  
Urea Cycle ◽  
Acute Phase Proteins ◽  
Phase Response ◽  
Mrna Levels ◽  
Urea Synthesis ◽  
Cycle Enzyme ◽  
Tnf Α ◽  
Urea Cycle Enzyme

The acute-phase response is a catabolic event involving increased waste of amino-nitrogen (N) via hepatic urea synthesis, despite an increased need for amino-N incorporation into acute-phase proteins. This study aimed to clarify the regulation of N elimination via urea during different phases of the tumor necrosis factor-α (TNF-α)-induced acute-phase response in rats. We used four methods to study the regulation of urea synthesis: We examined urea cycle enzyme mRNA levels in liver tissue, the hepatocyte urea cycle enzyme proteins, the in vivo capacity of urea-N synthesis (CUNS), and known humoral regulators of CUNS at 1, 3, 24, and 72 h after TNF-α injection (25 μg/kg iv rrTNF-α) in rats. Serum acute-phase proteins and their liver mRNA levels were also measured. The urea cycle enzyme mRNA levels acutely decreased and then gradually normalized, whereas the urea cycle enzyme proteins remained essentially unchanged over time. The CUNS rose after 3 h and then normalized. The acute-phase response was fully activated at 24 h with markedly increased serum levels of the acute-phase proteins. TNF-α acutely upregulated the CUNS. Later, despite the fully established 24-h acute-phase response and the decreased activity of the urea cycle enzyme genes, there was no change in the urea cycle enzyme proteins or the CUNS. Thus in no phase after the initiation of the acute-phase response was in vivo urea synthesis orchestrated in combination with acute-phase protein synthesis so as to limit N waste.

scholarly journals Effects of LPS on transport of indocyanine green and alanine uptake in perfused rat liver

1999 ◽  
Vol 277 (1) ◽  
pp. G91-G100 ◽  
Author(s):  
Mette Lund ◽  
Leslie Kang ◽  
Niels Tygstrup ◽  
Allan W. Wolkoff ◽  
Peter Ott
Keyword(s):  
Indocyanine Green ◽  
Rat Liver ◽  
Acute Phase ◽  
Acute Phase Response ◽  
Organic Anion ◽  
Hepatic Uptake ◽  
Phase Response ◽  
Isolated Perfused Rat Liver ◽  
Perfused Rat Liver ◽  
Tnf Α

Lipopolysaccharide (LPS) initiates cholestasis. Whether this process is mediated by tumor necrosis factor-α (TNF-α) and whether the cholestatic response to LPS is associated with intrahepatic accumulation of possibly toxic substances are under debate. To study these questions the hepatic uptake and biliary excretion of indocyanine green (ICG) was examined in the isolated perfused rat liver 18 h after intravenous treatment of rats with either saline, 1 mg/kg body wt LPS, or LPS and intraperitoneal pentoxifylline (POF) ( n = 6 in each group). POF inhibits TNF-α release after LPS administration. LPS induced a typical acute-phase response with increased mRNA for acute-phase proteins, reduced albumin mRNA, and increased hepatic uptake of alanine. Intrinsic hepatic clearance of ICG in controls (1.01 ± 0.05 ml ⋅ min−1 ⋅ g liver−1) was similarly decreased by LPS alone (0.62 ± 0.04 ml ⋅ min−1 ⋅ g−1; P = 0.002 vs. control) or combined with POF (0.66 ± 0.06 ml ⋅ min−1 ⋅ g−1). A kinetic analysis indicated that LPS reduced both uptake and excretion processes in a balanced manner, so that intrahepatic ICG content was unaffected or even slightly reduced, as confirmed by measurement of ICG contents in the perfused livers. In livers from parallel-treated nonperfused rats, mRNA for the organic anion transporting protein-1 (Oatp1, which is likely to mediate ICG uptake) was unaffected by LPS, whereas the concentration of Oatp1 protein was reduced. Thus LPS induced an acute-phase response that included downregulation of ICG uptake by reduction of Oatp1 protein concentration, possibly at a posttranscriptional level. TNF-α appears not to be the mediator because POF did not modify these LPS effects.

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