Increase In Serum Amyloid A Research Articles

Adipokines, Inflammation, and Visceral Adiposity across the Menopausal Transition: A Prospective Study

Postmenopausal women have greater visceral adiposity compared with premenopausal women. Adipokines are associated with increased adiposity, insulin resistance, and atherosclerosis. The objective of the study was to assess changes in adipokines and inflammatory markers through the menopausal transition and correlate them with changes in visceral adiposity. This was a prospective cohort study of women through the menopausal transition conducted at the University of Washington. Sixty-nine healthy women were followed up longitudinally from premenopausal (aged 45-55 yr) to postmenopausal status (aged 49-60 yr). On premenopausal and postmenopausal visits, fasting blood was drawn for adiponectin, leptin, serum amyloid A (SAA), C-reactive protein (CRP), monocyte-chemotactic protein-1, tissue plasminogen activator antigen (tPA), IL-6, and TNF-alpha. Body composition measures were assessed by body mass index, whole-body dual x-ray absorptiometry scan, and computed tomography scan of the abdomen at the lumbar 4-5 level. Women had a statistically significant increase in SAA, tPA, monocyte-chemotactic protein-1, and adiponectin between the two measurement occasions (P = 0.04, P = 0.02, P = 0.001, and P < 0.001, respectively). The increase in intraabdominal fat was correlated positively with the change in SAA (r = 0.31, P = 0.02), CRP (r = 0.56, P < 0.001), tPA (r = 0.40, P = 0.002), and leptin (r = 0.41, P = 0.002) and negatively correlated with the change in adiponectin (r = -0.37, P = 0.005). After adjustment for change in sc abdominal fat, the correlation between change in CRP, tPA, leptin, and adiponectin remained significantly associated with change in intraabdominal fat. Women going through the menopausal transition have deleterious changes in inflammatory markers and adipokines that correlate with increased visceral adiposity.

Acute Phase Protein Response in Goats

Acute phase proteins (APPs) are important diagnostic indicators of inflammatory disturbances in animals. The objectives of the current study were to validate analytical methods for measuring haptoglobin (Hp), serum amyloid A (SAA), acid soluble glycoprotein (ASG), fibrinogen, and albumin concentrations in goats and to evaluate their response to an inflammatory stimulus in this species. Intra- and interassay coefficients of variation (CVs) were in the range 0.07-9.31% and 1.83-12.68%, respectively, for all APPs and showed good precision. All assays determined APPs in a linear manner at different sample dilutions with high correlation coefficients with the exception of fibrinogen, which was measured by the heat precipitation method. Subcutaneous injection of turpentine oil induced an increase in Hp, SAA, ASG, and fibrinogen serum concentrations and a decrease in albumin concentration.

Acute phase protein response in dogs with experimentally induced gastric mucosal injury

The acute phase response is part of the innate defense system of an animal against trauma, inflammation, and infection. The purpose of this investigation was to evaluate the acute phase response in dogs with acetylsalicylic acid-induced gastric mucosal injuries and to determine its potential diagnostic significance. Ten, healthy, cross-breed dogs (6 females and 4 males) were given oral acetylsalicylic acid in a single oral dose of 200 mg/kg for the experimental model of acute gastric mucosal injury. Heparinized blood samples were collected before (day 0) and on days 1, 4, and 7 after acetylsalicylic acid administration to determine plasma C-reactive protein (CRP), serum amyloid-A (SAA), haptoglobin, fibrinogen, total protein, albumin, and iron concentrations. Total WBC counts were done in whole blood. Endoscopy was done on each of the selected days, and gastric lesions were scored and localized. Hemorrhagic linear erosions were found in all dogs on day 1, concurrent with significant increases in CRP, SAA, haptoglobin, and fibrinogen concentrations, and in WBC counts; however, iron concentration was decreased. Peak haptoglobin and fibrinogen concentrations occurred on day 4, at which time only nonhemorrhagic lesions were observed endoscopically. On day 7, results for all analytes except haptoglobin had returned to baseline levels, along with resolution of most gastric lesions. Results of this study indicate that a rapid acute phase protein response occurs after induced gastric mucosal injury in dogs and may be potentially useful together with gastroscopy in the diagnosis and monitoring of gastric injury.

Minimal invasiveness of radical laparoscopic prostatectomy: dreams or reality?

To determine the systemic response to extraperitoneal laparoscopic (eLRP) and open retropubic radical prostatectomy (RRP). Materials and Methods. In all, 430 patients who had eLRP (200) or open RRP (230) were recruited; patients in both groups had similar preoperative staging. In addition to peri-operative variables (operative duration, complications, blood loss, transfusion rate, hospitalization, catheterization), oncological data (Gleason score, pathological stage, positive margins) were also compared. The extent of the systemic response to surgery-induced tissue trauma was measured in all patients, by assessing the levels of acute-phase markers C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6) and IL-10 before, during and after RP. Results. The duration of surgery, transfusion rate, hospital stay and duration of catheterization were comparable with those of previous studies. There was an increase in IL-6, CRP and SAA but no change in IL-10, and no differences between eLRP and RRP over the entire period assessed. Conclusion. The invasiveness of eLRP could not be substantiated objectively on the basis of the variables measured in this study. The surgical trauma and the associated invasiveness of both methods were equivalent.

Type I IL-1 Receptor Mediates IL-1 and Intracellular IL-1 Receptor Antagonist Effects in Skin Inflammation

The IL-1 system plays a key role in skin physiology and pathology. In this study, we used mutant mice lacking the type I IL-1 receptor (IL-1RI), lacking IL-1 receptor antagonist (IL-1Ra), or overexpressing the human intracellular (ic) IL-1Ra1 isoform, as well as combinations thereof, to dissect the role of the IL-1 system in phorbol 13-myristate 12-acetate (PMA)-induced skin inflammation. In wild-type (WT) mice, PMA application induced epidermal thickening and dermal inflammation. Skin IL-1alpha production and circulating levels of the acute-phase protein serum amyloid A (SAA) were elevated. In mice lacking IL-1RI or overexpressing icIL-1Ra1, PMA induced similar epidermal thickening as in WT mice, but dermal inflammation was partially prevented. Skin IL-1alpha mRNA expression was similar in PMA-treated IL-1RI-/- and WT mice, whereas the increase in serum SAA was suppressed in IL-1RI-/- mice. Interestingly, PMA-induced IL-1alpha mRNA expression was further enhanced by icIL-1Ra1 overexpression in an IL-1RI-dependent manner. Finally, IL-1Ra-/- mice spontaneously displayed skin lesions characterized by high IL-1beta, but not IL-1alpha, expression. In conclusion, PMA-induced epidermal thickening and skin IL-1alpha expression were independent of IL-1 signaling, in contrast to dermal inflammation and systemic inflammatory response.

Prospective non‐randomized evaluation of four mediators of the systemic response after extraperitoneal laparoscopic and open retropubic radical prostatectomy

To report a prospective, controlled, non-randomized patient study to determine the systemic response to extraperitoneal laparoscopic (eLRP) and open retropubic radical prostatectomy (RRP). In all, 403 patients who had eLRP (163) or open RRP (240) were recruited; patients in both groups had similar preoperative staging. In addition to peri-operative variables (operative duration, complications, blood loss, transfusion rate, hospitalization, catheterization), oncological data (Gleason score, pathological stage, positive margins) were also compared. The extent of the systemic response to surgery-induced tissue trauma was measured in all patients, by assessing the levels of acute-phase markers C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6) and IL-10 before, during and after RP. The duration of surgery, transfusion rate, hospital stay and duration of catheterization were comparable with those in previous studies. There was an increase in IL-6, CRP and SAA but no change in IL-10, and no differences between eLRP and RRP over the entire period assessed. The invasiveness of eLRP could not be substantiated objectively based on the variables measured in this study. The surgical trauma and associated invasiveness of both methods were equivalent.

Serum concentrations of adiponectin and serum amyloid A in patients with end-stage renal disease and following successful kidney transplantation

Objective Adiponectin (ADPN), a collagen-like protein of the collectin family produced by adipocytes, may play a crucial role in the association between inflammation, atherosclerosis, and IR. Plasma ADPN is also down-regulated in association with obesity-linked diseases including coronary artery diseases. Although reports have shown that ADPN increases during maintenance hemodialysis (HD) and decreases following successful renal transplantation, there is no evidence about whether ADPN causes the deterioration of vasculitis. Methods To determine if ADPN causes inflammation and insulin resistance, we examined the differences in serum concentrations of serum amyloid A (SAA), homeostasis model assessment value for insulin resistance (HOMA-R), and ADPN in patients who had undergone both maintenance HD and who had later received a renal transplant. Results The mean SAA (27.7 ± 8.3 g/mL) and ADPN (20.8 ± 11 g/mL) levels in the patients while they underwent HD were high. ADPN increased after an HD session (30.2 ± 10.5 g/mL). Patients with diabetes mellitus (DM) who had low ADPN concentrations of at least 20 g/mL had higher body mass index (BMI), HOMA-R, and SAA values. One month after the patients received kidney transplantation, plasma ADPN decreased to 15.2 ± 1.3 g/mL, and mean SAA increased (14.6 ± 4.8 vs. 89.5 ± 23.5 g/mL before and after treatment, respectively). Conclusions Both the serum ADPN and SAA levels of the patients while they underwent were high, and their ADPN levels decreased after successful kidney transplantation. Conversely, their SAA levels increased after kidney transplantation. These results suggest a correlation between ADPN level and vasculitis. Also, this is the first time it has been shown that ADPN and SAA increase simultaneously.

Inflammatory markers and in-hospital mortality in acute ischaemic stroke

Background There is substantial evidence that cerebral ischaemia triggers an inflammatory response. We examined the short-term prognostic value on mortality of C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) in patients with ischaemic stroke. Methods We recruited 203 consecutive patients, under the age of 66 years (mean age = 54.2 ± 8.1 years, men = 132) who admitted to the Neurology Department with the diagnosis of non-haemorrhagic stroke. Patients in atrial fibrillation or with evidence of inflammatory or malignant disease were excluded. The diagnosis was confirmed with a computed tomography or magnetic resonance imaging of the brain within 24 h of admission. CRP, IL-6 and SAA levels were determined within 12 h from admission. Results Fourteen (6.9%) patients died during hospitalization. Serum concentrations of CRP, IL-6 and SAA were significantly higher in patients who died compared with those who survived and were independently associated with early death, after adjusting for various confounding factors. For one unit increase in IL-6, CRP and SAA there was an 18%, 14% and 9% higher risk of dying during hospitalization, respectively. Comparisons of the areas under the ROC curve showed that IL-6 had the best predictive ability. Age-adjusted cut-off point analysis showed that IL-6 levels >13 pg/ml were the optimal point that discriminated those who died from the rest of the patients (sensitivity = 85% and specificity = 93%). Conclusions We demonstrated that in-hospital mortality in ischaemic stroke is associated with an exacerbation of inflammatory response as it is reflected by the higher serum levels of IL-6, CRP and SAA. From the inflammatory markers high IL-6 levels had the strongest independent predictive value for in-hospital mortality.

Preliminary Studies of Serum Acute-Phase Protein Concentrations in Hematologic and Neoplastic Diseases of the Dog

Serum concentrations of acute-phase proteins (APPs): haptoglobin (Hp), ceruloplasmin (Cp), serum amyloid A (SAA), and C-reactive protein (CRP) were determined in healthy dogs (n = 15) and dogs with different diseases grouped as acute inflammation (I, n = 12), hematologic neoplasias (HT, including leukemia and lymphoma, n = 16), nonhematologic neoplasias (NHT, including epithelial, mesenchymal, and mixed, n = 20), and autoimmune hemolytic anemia (AIHA, n = 8). SAA and CRP were analyzed using commercially available enzyme-linked immunosorbent assay (ELISA) kits, and Hp and Cp were measured using colorimetric methods, all previously validated for use in dogs. Increased concentrations of all APPs were observed in all groups of diseased dogs, but statistical significance only was observed with Hp (I, P < .001; HT, P < .05), Cp (I, P < .05; AIHA, P < .01), and CRP (I, P < .001; HT, P < .001; AIHA, CRP P <.05). High variability in individual APPs within each group of diseases was found with no significant differences between leukemia and lymphoma as well as among different types of neoplasia. The AIHA group had smaller increases in Hp, SAA, and CRP but higher concentrations of Cp. When follow-up of individual cases was possible, a decrease in APPs generally was found in cases with favorable outcome. The results of this study suggest that neoplasia and hematologic diseases such as AIHA should be considered as possible causes of mild increases in APPs in dogs. Measurement of APPs may be helpful to assess clinical evolution and monitor treatment of these processes.

Cholesterol Feeding Increases C-Reactive Protein and Serum Amyloid A Levels in Lean Insulin-Sensitive Subjects

Inflammatory markers associated with elevated cardiovascular risk are increased by cholesterol feeding in animal models. However, whether dietary cholesterol increases inflammatory marker levels in humans is not known. C-reactive protein (CRP), serum amyloid A (SAA), and lipoprotein levels were compared in 201 healthy subjects on an American Heart Association-National Cholesterol Education Program step 1 diet at baseline and after addition of 4 eggs per day for 4 weeks. Subjects were classified a priori into 3 groups based on their body mass index (BMI) and insulin sensitivity index (SI): lean insulin sensitive (LIS), mean+/-SEM BMI, 23.2+/-0.3 kg/m2, and SI, 6.7+/-0.3x10(-4)min(-1)/(microU/mL), n=66; lean insulin resistant (LIR), BMI, 24.5+/-0.2 kg/m2 and SI, 2.9+/-0.1x10(-4)min(-1)/(microU/mL), n=76; or obese insulin resistant (OIR), BMI, 31.4+/-0.5 kg/m2 and SI, 2.1+/-0.1x10(-4)min(-1)/(microU/mL), n=59. Insulin resistance and obesity each were associated with increased baseline levels of both CRP (P for trend, <0.001) and SAA (P for trend=0.015). Egg feeding was associated with significant increases in both CRP and SAA in the LIS group (both P<0.01) but not in the LIR or OIR groups. Egg feeding also was associated with a significant increase in non-HDL cholesterol (P<0.001) in LIS subjects; however, there was no correlation between the change in non-HDL cholesterol or changes in either CRP or SAA in this group. A high-cholesterol diet leads to significant increases in both inflammatory markers and non-HDL cholesterol levels in insulin-sensitive individuals but not in lean or obese insulin-resistant subjects.

Maternal and Cord Blood Levels of Serum Amyloid A, C‐Reactive Protein, Tumor Necrosis Factor‐α, Interleukin ‐1β, and Interleukin‐8 During and After Delivery

C-reactive protein (CRP) and serum amyloid A (SAA) are acute-phase proteins mainly synthesized by the liver in response to some cytokines. They are potentially useful to diagnosing infection and monitoring different clinical conditions. The aim of this study was to measure SAA and CRP in maternal and cord blood during and after delivery and try to correlate these proteins with tumor necrosis factor-α , interleukin-1β, and interleukin-8. Acute-phase proteins and cytokines were measured by ELISA in 24 healthy pregnant women undergoing vaginal delivery or Cesarean section. Cord blood samples in addition to maternal blood were collected. SAA and CRP reached the maximum maternal serum levels 24 hours after delivery, while cytokines remained constant over time. SAA and CRP were significantly higher in maternal serum than in newborn's (P < .001) at the moment of delivery. SAA and CRP, regardless of the type of delivery, reproduce the common pattern observed in most inflammatory conditions. Proinflammatory cytokine serum levels do not mirror the increase in SAA and CRP levels.

Preliminary Studies of Serum Acute-Phase Protein Concentrations in Hematologic and Neoplastic Diseases of the Dog

Serum concentrations of acute-phase proteins (APPs): haptoglobin (Hp), ceruloplasmin (Cp), serum amyloid A (SAA), and C-reactive protein (CRP) were determined in healthy dogs (n = 15) and dogs with different diseases grouped as acute inflammation (I, n = 12), hematologic neoplasias (HT, including leukemia and lymphoma, n = 16), nonhematologic neoplasias (NHT, including epithelial, mesenchymal, and mixed, n = 20), and autoimmune hemolytic anemia (AIHA, n = 8). SAA and CRP were analyzed using commercially available enzyme-linked immunosorbent assay (ELISA) kits, and Hp and Cp were measured using colorimetric methods, all previously validated for use in dogs. Increased concentrations of all APPs were observed in all groups of diseased dogs, but statistical significance only was observed with Hp (I, P < .001; HT, P < .05), Cp (I, P < .05; AIHA, P < .01), and CRP (I, P < .001; HT, P < .001; AIHA, CRP P < .05). High variability in individual APPs within each group of diseases was found with no significant differences between leukemia and lymphoma as well as among different types of neoplasia. The AIHA group had smaller increases in Hp, SAA, and CRP but higher concentrations of Cp. When follow-up of individual cases was possible, a decrease in APPs generally was found in cases with favorable outcome. The results of this study suggest that neoplasia and hematologic diseases such as AIHA should be considered as possible causes of mild increases in APPs in dogs. Measurement of APPs may be helpful to assess clinical evolution and monitor treatment of these processes.

Acute phase response in reindeer after challenge with Escherichia coli endotoxin

The serum concentrations of two acute phase proteins (APPs), haptoglobin (Hp) and serum amyloid-A (SAA), were monitored in reindeer after challenge with endotoxin. Four adult female reindeer received either 0.1 μg/kg Escherichia coli 0111:B4 lipopolysaccharide B or saline solution intravenously. At the second challenge, the treatments were reversed. In addition to the APPs, changes in blood chemistry and rectal temperature were monitored. The endotoxin challenge caused a significant increase in SAA (peak 48 h) and a sharp decrease (8–12 h) of serum iron concentrations in all animals. The mean Hp concentration increased at 8 h and remained elevated until 48 h, but no statistically significant differences were found. This investigation demonstrates that challenge with a single-bolus dose of E. coli endotoxin can activate the acute phase response (APR) and SAA appears to be a more sensitive indicator of the APR than Hp during bacterial infection in reindeer.

Haptoglobin and serum amyloid A in milk and serum during acute and chronic experimentally induced Staphylococcus aureus mastitis.

Local and systemic changes in the acute phase proteins, haptoglobin and serum amyloid A (SAA), were studied in six dairy cows during the acute and chronic phases of experimentally induced Staphylococcus aureus mastitis. Haptoglobin and SAA were measured in serum, and in milk from infected and healthy control udder quarters within each cow. Concentrations of haptoglobin and SAA increased rapidly in both serum and milk during the acute phase of mastitis and followed a similar pattern. Significantly raised milk concentrations of SAA were also found during chronic subclinical mastitis. Serum concentrations of SAA also tended to be higher during the chronic phase than pre-infection. Increases in milk haptoglobin and SAA were specific for the infected udder quarters. In conclusion, measurement of SAA in milk samples could be a useful tool in diagnosing mastitis.

Developmental regulation of expression of rabbit C-reactive protein and serum amyloid A genes

Serum amyloid A (SAA) and C-reactive protein (CRP) are acute phase plasma proteins which increases 100- to 1000-fold after inflammatory stimuli. In this study pregnant rabbits were given lipopolysaccharide (LPS) or subjected to laparotomy with fetal injections of LPS at different stages of gestation. Newborn rabbits were given LPS or saline, SAA and CRP mRNA were studied using Northern blot analyses and scanning densitometry. In vitro transcribed RNAs were used as standards for quantitative mRNA analyses. A gradual increase in LPS-induced SAA and CRP mRNA levels was observed during development, but only SAA mRNA induction was seen at gestational day 19. Fetal SAA and CRP mRNA induction was not seen after maternal LPS stimulation. The constitutive level of SAA and CRP mRNA was significantly lower in fetal rabbits than in adults. The control level of SAA mRNA in one-day-old rabbits was higher than the normal adult level, while the neonatal CRP mRNA level was lower. SAA2 seemed to be the major acute phase reactant in both fetal, neonatal and adult rabbits, while relatively more SAA3 was found during early developmental stages. The study demonstrated that CRP and three SAA genes are differentially regulated during development.

Induction of acute phase proteins in mice and humans by treatment with AS101, an immunomodulator with radioprotective properties

AS101 (ammonium trichloro(dioxyethylene-0,0′)tellurate) is a new synthetic compound previously described by us as having immunomodulating properties and minimal toxicity. Phase II clinical trials are currently in progress with AS101 on cancer patients. AS101 has been recently found to have both radioprotective and chemoprotective effects on hemopoiesis of irradiated mice or mice treated with various chemotherapeutic drugs. The present research was designed to study the in vivo induction of liver acute phase proteins secretion in mice or patients treated with AS101. Induction of these proteins, some of which have the capacity to scavenge free radicals, may contribute to radioprotection. We present evidence that treatment with the immunomodulator AS101 increases production of a variety of acute phase proteins. We demonstrate a significant elevation of serum amyloid A (SAA) in sera of treated mice, as well as an increase in SAA, factor B and ceruloplasmin in sera of patients treated with AS101. The same AS101 treatment was shown to decrease the amount of the negative acute phase protein, albumin. In addition we show that IL-1, IL-6 and TNF-α are important mediators of changes in SAA concentrations induced by AS101. Abrogation of SAA production in AS101 treated mice by any one of the and IL-1R, IL-6R or TNF-α antibodies indicates that at least in mice, SAA production is not controlled by a single extracellular signal, but rather it is regulated, at the least, by all three cytokines in various combinations. A better understanding of the mechanism by which AS101 confers radioprotection will enable us to use it more effectively in the restoration of hemopoiesis in patients following radiation or suffering from overdose or accidental radiation.

Amyloid A fibril degrading activity in serum in liver disease — relation to serum acute phase and other protein levels

Human serum contains amyloid A degrading activity. This activity is decreased in patients with reactive systemic amyloidosis. To study the specificity of this finding, we evaluated the effect of liver disease per se on the amyloid degrading activity in serum as well as its relation to serum amyloid A (SAA), the putative precursor of amyloid A fibrils, and other serum protein levels in alcoholic and non-alcoholic non-malignant liver diseases without signs of amyloidosis. The amyloid A-degrading activity was significantly decreased in liver cirrhosis. The lowest activity was seen in patients with advanced cirrhosis. There was a positive correlation between the degradative activity and indices of hepato-cellular synthetic function (serum albumin, r = 0.77; serum prealbumin, r = 0.65). Most of the patients with liver disease had a detectable SAA level; 77% had a level higher than 5 mg/l (compared to 12% among blood donors). However, the SAA increase was generally only slight, e.g. in alcoholic liver cirrhosis the median SAA level was 15 mg/1. The results show that liver dysfunction per se decreases amyloid A-degrading activity in serum. A reduced activity cannot therefore be regarded as specific for reactive amyloidosis. Since reactive amyloidosis is extremely rare in liver cirrhosis, it seems obvious that a reduced amyloid degrading activity alone, in the absence of a markedly elevated SAA level, does not predispose, at least in patients with liver disease, to amyloidosis.