Negative Acute Phase Proteins Research Articles

Serum Acute Phase Protein Concentrations in Female Dogs with Mammary Tumors

Acute phase proteins (APPs) are proteins whose concentrations in serum change after any inflammatory stimulus or tissue damage. The aim of the current study was to evaluate 3 positive APPs (C-reactive protein, serum amyloid A, and haptoglobin) and 1 negative APP (albumin) in female dogs with mammary neoplasia. Acute phase proteins were studied in 70 female dogs aged 8-12 years in the following groups: healthy (n = 10); mammary tumors in stages I (n = 19), II (n = 5), III (n = 6), IV (n = 5), and V (n = 7); and with mammary neoplasia plus a concomitant disease (n = 18). In animals with mammary neoplasia, significant increases of positive APPs were only detected in those that had metastasis or a neoplasm with a diameter greater than 5 cm and ulceration. Dogs with mammary neoplasia and a concomitant disease also had high C-reactive protein concentrations. Albumin concentration was decreased in animals with metastasis and with a concomitant disease. The results of the present study indicate that the acute phase response could be stimulated in female dogs with mammary gland tumors because of different factors, such as metastasis, large size of the primary mass, and ulceration or secondary inflammation of the neoplasm.

Acid hydrolysis followed by matrix‐assisted laser desorption/ionization mass spectrometry for the rapid diagnosis of serum protein biomarkers in patients with major depression

We have developed a technique combining acid hydrolysis with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for the rapid study of the changes in the levels of positive and negative acute phase protein biomarkers in the sera of patients suffering from major depression. The serum proteins were first precipitated using an organic solvent; after separation, they were subjected to hydrochloric acid hydrolysis (6 M HCl) for 10 min. The resulting peptides were characterized using MALDI-TOF MS. Short-term treatment of the serum proteins with HCl efficiently removed interference from the abundant protein - albumin - and produced abundant peptide ion signals in the range of m/z 4000-10 000. This approach allowed us to rapidly detect the peptide ions originating from transferrin (a common negative acute phase protein) and fibrinogen (a common positive acute phase protein). The average ratios and (standard deviations) of the ion signals derived from transferrin/fibrinogen were 3.58 (+/-1.93) for the healthy control subjects and 1.02 (+/-0.52) for the patients suffering from major depression. The differences in transferrin/fibrinogen ratios between healthy controls and patients suggest that major depression will induce internal inflammation and cause either an increase in the level of fibrinogen or a decrease in the level of transferrin.

Serum Amyloid-A Rather Than C-Reactive Protein Is a Better Predictor of Mortality in Hemodialysis Patients

The most frequent cause of death in hemodialysis patients is cardiovascular disease with chronic inflammation being an epidemiologically proved risk factor. Many studies have shown C-reactive protein (CRP) as the strongest predictor of long-term mortality of hemodialysis patients, while other reports have indicated acute phase proteins as potential predictors of the mortality. The present study therefore aimed to evaluate the prevalence of chronic inflammation in hemodialysis patients and the role of acute phase proteins together with lipids and divalent ions for predicting mortality in hemodialysis patients. Chronic inflammation was defined, based on the serum level of high sensitive CRP > 8.4 mg/L and/or serum amyloid-A (SAA) > 8.9 mg/L. Acute phase proteins are defined as one whose plasma concentration increase (positive) or decreases (negative) by at least 25% during inflammation. High sensitive CRP and SAA were positive acute phase proteins measured, while albumin and fetuin-A, a calcification inhibitor, were selected as negative acute phase proteins. This prospective 36-month follow-up study included 130 patients (60 males and 70 females, aged 55.1 +/- 12.9 years) maintained by hemodialysis for 107.2 +/- 54.72 months at a Nephrology Clinic in Belgrade. The prevalence of chronic inflammation was 35.4% (46 patients). During the follow-up period, 24 patients (18.5%) died and 2 patients received transplants. In multivariate analysis, potential independent predictors of mortality in hemodialysis patients are hyperphosphatemia, hypoalbuminemia, and high SAA. Considering that assays for SAA are widely used, we propose that SAA is the best predictor for outcomes of end-stage renal disease.

Identification of connective tissue growth factor as a hepatic negative acute phase protein

Identification of connective tissue growth factor as a hepatic negative acute phase protein

Acute-phase protein response in pigs experimentally infected with Haemophilus parasuis

The acute-phase protein (APP) response to an infection caused by Haemophilus parasuis, the etiological agent of Glässer's disease in pigs, was characterized measuring serum concentrations of pig major acute-phase protein (pig MAP), haptoglobin (HPT), C-reactive protein (CRP) and apolipoprotein A-I (ApoA-I) in colostrum-deprived pigs. They were divided into six experimental groups: non-immunized control group (I); immunized with a non-commercial bacterin (II); with an OMP-vaccine (III); with a sublethal dose (IV); and with two commercial bacterins (V and VI). All groups were challenged intratracheally with 5 × 10(9)CFU of H. parasuis 37 days after immunisation. The highest levels of the positive APPs (pig MAP, HPT and CRP) and the lowest levels of the negative APPs (ApoA-I) were observed in the animals that died as a consequence of the infection, both those in the non-immunized and in the immunized groups. However, the surviving animals (all of them in groups II, V and VI, two pigs in group III, and three in group IV) showed a minor variation in APP response, mainly on day 1 post-challenge (p.c.), and then tended to recover the initial values. APP response was still less pronounced in the groups of pigs previously immunized with bacterins. In conclusion, APP response can reflect Glässer-disease ongoing, showing a correlation between the severity and duration of the clinical signs and lesions and the magnitude of changes in the APP levels.

Suppressed acute phase response to LPS-induced hepatic injury in Smad3-deficient mice

The generation of animals lacking Smad proteins has made it possible to explore the contribution of the TGF-β-Smad signaling to immune activity in vivo. And there have been related issues actively pursued by many laboratories. Here we report that, in contrast to the markedly enhanced inflammatory response, Smad3 gene knockout ( Smad3 ex8/ex8) mice paradoxically show suppressed hepatic acute phase response to the injury induced by lipopolysaccharide (LPS) compared with wild-type mice, characterized by significantly weaker reaction of several typical acute phase proteins in mRNA level. The increase of positive acute phase proteins, e.g. α1-acid glycoprotein (α1-AGP), haptoglobin (HP) and C-reaction protein (CRP), and the decrease of negative acute phase proteins, including albumin (ALB) and transferrin (TRF), were both repressed according to the expression in liver estimated by optimized RT-PCR. Smad3 ex8/ex8 mice also exhibited lower survival rate as stimulated by LPS, which was probably on account of the suppressed acute phase response. These data are, to our knowledge, the first to implicate Smad3 in specific pathways of acute phase response in the liver.

Low serum fetuin‐A concentration predicts poor outcome only in the presence of inflammation in prevalent haemodialysis patients

Fetuin-A, a negative acute phase protein that inhibits vascular calcification, has a controversial association with mortality in chronic kidney disease (CKD) patients. Chronic inflammation, which is common in CKD, may promote vascular calcification. We investigated the impact of inflammation on the relationship between serum fetuin-A and mortality (42 months) in 222 prevalent haemodialysis (HD) patients. Serum fetuin correlated negatively with comorbidity score (assessed by Davies score) and circulating inflammatory markers. Patients with low fetuin-A levels (< median) had higher mortality (Hazard ratio 'HR' 2.2; CI 1.4-3.5, P < 0.001), but this association was lost after adjustment for age, gender, comorbidities score, dialysis vintage and inflammation (CRP > median). In inflamed patients with low fetuin a significantly independent association with mortality (HR 2.3; CI 1.2-4.5, P = 0.01) was observed compared to non-inflamed patients with high fetuin-A, after adjusting for the same variables. Non-inflamed patients with low fetuin-A and inflamed patients with high fetuin-A did not have increased mortality compared to non-inflamed patients with high fetuin-A. The results show that low levels of serum fetuin-A are associated with increased mortality in HD patients only in the presence of inflammation. This suggests that coexistence of a low serum fetuin-A level and low-grade inflammation exerts an additive effect on the risk of death in HD patients.

Effects of Inflammatory Conditions on Liver Activity in Puerperium Period and Consequences for Performance in Dairy Cows

The relationship between inflammation and general health conditions in dairy cows and the link between inflammation, liver function, and fertility are poorly understood. To clarify these relationships, 120 multiparous dairy cows were followed throughout an entire lactation. Blood samples were collected during the first month of lactation for a metabolic profile, and milk yield, disease occurrence, and fertility parameters were monitored during the entire lactation. Twenty-four cows were culled, and another 19 were excluded because they had serious problems after 30 d in milk (DIM) and before the first insemination. The remaining 77 cows were pregnant at the end of lactation and were retrospectively grouped into quartiles based on liver activity index (LAI), which is based on plasma negative acute phase proteins. Cows in the lower (LO) and intermediate lower (INLO) quartiles of LAI had more severe inflammations with high concentrations of haptoglobin (0.77 and 0.61g/L) and globulin (42.5 and 39.0g/L), respectively, during the first week of lactation compared with cows in the upper (UP) and intermediate upper (INUP) quartiles of LAI (haptoglobin: 0.28 and 0.45g/L, and globulin: 34.2 and 36.9g/L, respectively). At 7 DIM, the cows in LO and INLO had greater bilirubinemia (8.7 and 10.5 vs. 6.3μM/L in UP) and lower blood urea (3.5 and 3.7 vs. 4.1mM in UP). The INLO group exhibited more days open (139 vs. 93) and services per pregnancy (2.68 vs. 1.65), but lower milk yield (38.3 vs. 40.8kg/d at 28 DIM) compared with UP. The LO group did not have a significantly lower fertility status, but presented the lowest milk yield (34.1kg/d at 28 DIM). Our data suggest that cows with lower LAI scores had a more pronounced inflammatory status during the first month of lactation, an impairment of usual hepatic functions (e.g., bilirubin clearance), and a larger negative energy balance. The same cows had poorer performance (lower milk yield and fertility) than cows with higher LAI scores. Overall data suggest that any effort to avoid the acute phase response in the transition period would be useful for optimizing the productive and reproductive performance of high-yielding dairy cows.

Different types of tea products attenuate inflammation induced in Trypanosoma brucei infected mice

An in vivo study was carried out to determine the effect of different types of Kenyan tea extracts on male Swiss albino mice infected with Trypanosoma brucei brucei isolate KETRI 2710. The isolate produced a similar clinical picture after a pre-patent period of 5 days post-infection (DPI). Parasitemia levels in the untreated mice and those given different teas developed exponentially at similar rates reaching similar densities at the peak of parasitemia 8 DPI. Between 9 and 13 DPI parasitemia decreased more rapidly in tea treated compared to the untreated mice which indicated that tea lowered parasitemia level. Anaemia indicated by a fall in erythrocyte packed cell volume (PCV) occurred within 4 DPI and remained below the normal levels until the terminal stages of the disease. A significant difference ( P < 0.05) was observed 11 DPI between the tea treated and the untreated mice indicating that tea enhanced resistance to erythrocyte destruction. Mice treated with tea exhibited significantly ( P < 0.01) reduced parasite-induced hypoalbuminemia as compared to the untreated. Since albumin is a negative acute phase protein, it shows a decrease during inflammatory conditions and therefore its elevation in the mice given tea in this study clearly demonstrated that tea ameliorated inflammation induced by T. b. brucei. Although green and white teas were superior in most of these characteristics, black tea, which is the principle tea product from Kenya, displayed remarkable properties some even comparable to those of green tea. Interestingly, tea was more efficacious than dexamethasone an established anti-inflammatory drug, demonstrating its therapeutic potential.

Altered protein metabolism following coronary artery bypass graft (CABG) surgery

The aim of the present study was to investigate the acute effect of CABG (coronary artery bypass graft) surgery on the rates of synthesis of muscle protein, the positive acute-phase protein fibrinogen and the negative acute-phase protein albumin. Synthesis rates of muscle protein, fibrinogen and albumin were measured simultaneously before and 4 h after the end of surgery from the incorporation of L-[(2)H(5)]phenylalanine (given at 43 mg/kg of body weight) in 12 patients undergoing CABG surgery. Surgery was performed either with the use of extracorporeal circulation with cardiopulmonary bypass (on-pump; n=5) or with the beating heart procedure without cardiopulmonary bypass (off-pump; n=7). Post-surgical muscle protein fractional synthesis rates were decreased by 36+/-6.5% compared with pre-surgical values (1.59+/-0.10 compared with 0.97+/-0.08%/day respectively; P<0.001). In contrast, the synthesis rates of both fibrinogen (36+/-4 compared with 100+/-11 mg.day(-1).kg(-1) of body weight; P<0.0001) and albumin (123+/-12 compared with 178+/-19 mg.day(-1).kg(-1) of body weight; P<0.001) were both significantly increased after surgery. No significant differences were found between surgery performed with or without cardiopulmonary bypass. In conclusion, the results demonstrate that CABG surgery has a profound effect on protein metabolism, with a differential response of protein synthesis in muscle and liver.

A Combination of Behavioral and Physiological Indicators for Assessing Pig Welfare on the Farm

The purpose of this research was to identify pig welfare indicators that could help in recognizing stressful practices on farm. The study evaluated behavioral and physiological indicators (cortisol and negative acute phase proteins) in 2 groups of 20 female pigs 4 months old after a 48-hr transport. The first group (A) was transported at the end of May, the second (B) in June. Behavioral observations and blood collection occurred at arrival (D1) and 28 days later (D28). Compared with within-animal control samples obtained 28 days later, pigs of Group A had increased cortisol levels and decreased albumin concentrations after arrival. As demonstrated by lesion and behavior observations, the effect on cortisol and albumin was higher in Group B pigs after a tail-biting episode occurred. The study has reported no evidence of Retinol Binding Protein (RBP) in pigs. A method developed for swine RBP quantification found RBP strongly reduced in D28 samples of Group B, confirming it to be a negative protein in pigs. The suggested combination of physiological and behavioral indicators could provide useful information on the welfare state of an animal.

Inflammation-associated ADAMTS13 deficiency promotes formation of ultra-large von Willebrand factor

In a prospective, longitudinal study, we investigated the association between decreased ADAMTS13 activity and impaired hemostasis, as well as organ dysfunctions in patients with systemic inflammation due to extracorporeal cardiopulmonary circuit or with severe sepsis. Similar to negative acute phase proteins, ADAMTS13 activity declined stepwise according to the extent of inflammatory responses. A marked imbalance between ADAMTS13 activity and VWF antigen level was associated with the appearance of ultra-large VWF multimers in plasma, with organ dysfunction and lethality. Our data support the view that systemic inflammation results in an ADAMTS13 deficiency which activates hemostasis.

Antioxidants modulate the IL‐6 induced inhibition of negative acute‐phase protein secretion in HepG2 cells

Despite increasing evidence on the potential of dietary antioxidants in modulating the etiology of certain chronic diseases such as cancer and cardiovascular diseases, little is known about their beneficial role in acute-phase responses and inflammatory diseases. From this viewpoint the aim of this study was to investigate the effect of selected dietary antioxidants in modulating the secretion of negative acute-phase proteins caused by interleukin-6 (IL-6) in HepG2 cells. Cells were first stimulated with a fixed dose of IL-6 for 24 h then incubated for a further 8 h with varying concentrations of eight antioxidants, alpha-lipoic acid (LA), (-)-epicatechin (EC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin (EGC), (-)-epigallocatechin gallate (EGCG), alpha-tocopherol (TOC), ascorbic acid (AA) and N-acetylcysteine (NAC). The culture supernatants were assayed for transthyretin (TTR) and retinol binding protein (RBP) using ELISA. The data revealed that IL-6 significantly reduced TTR and RBP secretion compared with the basal production. All tested antioxidants attenuate the reduction in TTR and RPB levels. The strongest effects were achieved with the highest concentration of each antioxidant. The order of effect were LA > EGCG > ECG > TOC > EGC > EC > NAC > AA. In conclusion, these results provide evidence that the dietary antioxidants can play a fundamental role in inflammatory processes.

Rhipicephalus (Boophilus) microplus: Distinct acute phase proteins vary during infestations according to the genetic composition of the bovine hosts, Bos taurus and Bos indicus

Tick bites may trigger acute phase responses. Positive and negative acute phase proteins were measured in infested cattle genetically resistant and susceptible to ticks. During heavier infestations levels of haptoglobin increased significantly in susceptible bovines; levels of serum amyloid A increased in resistant bovines; levels of alpha-1-acid glycoprotein decreased significantly in resistant bovines; levels of transferrin decreased significantly in susceptible bovines. In conclusion, tick infestations trigger acute phase responses and enhancement of specific acute phase proteins differs according to the genetic composition of hosts. Acute phase proteins may constitute useful biological signatures for monitoring the stress induced by tick infestations.

Ação do prebiótico sobre as proteínas de fase aguda de pacientes com neoplasia hematológica

Os pacientes com neoplasias hematológicas são submetidos a tratamento quimioterápico que induz uma intensa alteração na integridade da mucosa intestinal, favorecendo um aumento da sua morbi-mortalidade. O presente trabalho foi desenvolvido na Unidade de Transplante de Medula Óssea do Centro de Pesquisas Oncológicas em Florianópolis - SC e teve como objetivo estudar a ação do prebiótico na resposta de proteína da fase aguda de pacientes com neoplasias hematológicas submetidos à quimioterapia. Foi realizado um estudo clínico randomizado duplo cego envolvendo 25 pacientes divididos em dois grupos que receberam por 15 dias: 12g de FOS (n=14) ou placebo (maltodextrina) (n=11). Todas as variáveis foram determinadas antes e após a suplementação. Foram avaliados os níveis séricos das proteínas de fase aguda negativas (albumina e pré-albumina) e a proteína de fase aguda positiva, proteína C reativa (PCR). Verificaram-se a presença de diarréia e de constipação, bem como a quantidade de bifidobactérias e valores de pH fecal. A redução dos níveis séricos de proteínas de fase aguda negativas (albumina e pré-albumina) comprovam o intenso catabolismo protéico, priorizando a síntese de proteína de fase aguda positiva (PCR). O grupo suplementado apresentou um aumento significante na quantidade de bifidobactérias e o pH fecal não foi alterado em ambos os grupos. Os níveis séricos de PCR foram estatisticamente superiores no grupo controle, indicando a ocorrência de processos inflamatórios e maior demanda metabólica, sugerindo que a quantidade de bifidobactérias pode ter favorecido a redução deste quadro no grupo suplementado, confirmado pela correlação negativa entre estas variáveis.

Plasma Paraoxonase, Health, Inflammatory Conditions, and Liver Function in Transition Dairy Cows

Paraoxonase (PON) is a liver protein with hydrolase activity that is released into the blood stream. Paraoxonase may serve as an index of liver function because it is drastically reduced in chronic liver damage. Sixty-seven periparturient dairy cows were used to evaluate the relationship between plasma PON, health problems, inflammatory conditions, and liver function. Baseline plasma PON concentrations during the first 30 d in milk (DIM) were retrospectively used to group cows into quartiles. Metabolic profile, lipid metabolites (e.g., nonesterified fatty acids, β-hydroxybutyrate), inflammatory indices (haptoglobin, ceruloplasmin), low and high density lipoprotein cholesterol, vitamin A, vitamin E, reactive oxygen metabolites, total antioxidants, and PON in plasma were measured 2 wk before to 8 wk after calving. Weekly milk yield, body condition score, and all health problems were recorded. After parturition (7 DIM), cows in the lower PON group had the lowest plasma concentrations of negative acute phase proteins compared with the higher PON group for retinol binding protein (23.2±2.86 vs. 36.0±2.96μg/dL of vitamin A), albumin (31.6±0.73 vs. 33.9±0.75 g/ L), total cholesterol (2.04±0.30 vs. 2.45±0.42 mmol/ L), and the highest concentrations of haptoglobin (0.67 vs. 0.24±0.03g/L; positive acute phase protein) and globulins (37.2 vs. 32.3±1.4g/L). Plasma bilirubin was highest in the cows (10.1 vs. 6.2±0.6μmol/L) in the lowest PON quartile. Plasma PON was negatively correlated with haptoglobin (r = −0.39) and bilirubin (r = −0.42) and positively correlated with retinol binding protein (r = 0.54), albumin (r = 0.38), and cholesterol (r = 0.55) fractions. A total of 82.3% of cows in the lower quartile and no cows in the upper quartile experienced serious inflammation. Lower quartile cows produced 28.1±10.3kg of milk/d; whereas upper quartile cows produced 38.3±7.7kg of milk/d during the first 30 DIM. A reduction in the ability of the liver to cope with the increased metabolic demand near parturition in dairy cows can be diagnosed using changes in baseline plasma PON.

Pig acute-phase protein levels after stress induced by changes in the pattern of food administration

A total of 240 pigs, 74 days old, half boars and half females, were included in a trial designed to assess the effect of the stress caused by changes in the pattern of food administration on the concentration of acute phase proteins (APP) and productive performance parameters. Half of the animals (pigs fed ad libitum, AL group) had free access to feed, while the rest were fed following a disorderly pattern (DIS group), in which animals had alternating periods of free access to feed and periods of no feeding, when food was removed from the feeder. The periods of free access to feed (two daily periods of 2-h duration) were randomly assigned, and varied from day to day. Total feed supplied per day was identical in both groups, and exceeded the minimal amount required for animals of these ages. Pen feed intake, individual body weights and the main positive pig APP pig major acute phase protein (Pig-MAP), haptoglobin, serum amyloid A (SAA), C-reactive protein (CRP), and the negative APP apolipoprotein A-I (ApoA-I) and transtherytin were determined every 2 weeks during the period 76 to 116 days of age. Animals fed ad libitum had better average daily gain (ADG) than DIS animals in the whole experimental period (P < 0.01) but the differences in ADG were only produced in the two first experimental sub-periods (60 to 74 and 74 to 116 days of age), suggesting that the stress diminished when the animals get used to the DIS feeding. Interestingly differences in ADG between DIS and AL pigs were due to males, whereas no differences were observed between females. The same differences observed for ADG were found for APP. DIS males had higher Pig-MAP concentration than AL males at 74 and 116 days of age, lower ApoA-I concentration at 74 days of age and higher haptoglobin and CRP concentration at 116 days of age (P < 0.05). The results obtained in this trial show an inverse relationship between weight gain and APP levels, and suggest that APP may be biomarkers for the evaluation of distress and welfare in pigs.

Decreased Levels of Circulating .ALPHA.2-Heremans-Schmid Glycoprotein/Fetuin-A (AHSG) in Patients with Rheumatoid Arthritis

Alpha2-Heremans Schmid glycoprotein/Fetuin-A (AHSG) is a circulating negative acute-phase protein, which inhibits bimineralization. It is often considered as a potential mediator between chronic inflammation and cardiovascular diseases. The metabolism of AHSG in patients with rheumatoid arthritis (RA) is unknown. Serum AHSG concentrations were measured in 102 patients with RA using a newly developed indirect enzyme-linked immunosorbent assay (ELISA). The serum AHSG levels in the RA patients were significantly lower than that in healthy volunteers (249.8 +/- 84.1 vs 425.0 +/- 93.0 microg/ml, P<0.0001). Serum C-reactive protein concentration and erythrocyte sedimentation rate were inversely correlated, while albumin, hemoglobin and total cholesterol were positively correlated with AHSG. Current serum AHSG levels did not affect the presence of aortic calcification, whereas cumulative glucocorticoid dosage was significantly related to aortic calcification (P=0.005). Serum AHSG levels were significantly decreased in patients with RA. The levels reflected inflammatory and malnutritional conditions. Its role in the development of cardiovascular diseases or inflammatory bone resorption remain uncertain in RA patients.

The porcine acute phase protein response to acute clinical and subclinical experimental infection with Streptococcus suis

The pig acute phase protein (APP) response to experimental Streptococcus suis ( S. suis) infection was mapped by the measurement of the positive APPs C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp) and major acute phase protein (pig-MAP) and the negative APPs albumin and apolipoprotein (Apo) A-I. The aim was to elucidate the differences in the acute phase behaviour of the individual APPs during a typical bacterial septicaemic infection. Pigs were inoculated subcutaneously with live S. suis serotype 2 and blood was sampled before and on various days post inoculation (p.i.), until the pigs were killed and autopsied on day 14 p.i. Clinical signs (fever and lameness) were observed in four of the five inoculated pigs from day 2 p.i., and these pigs also had arthritic lesions at autopsy. CRP and SAA showed fast increases in serum concentrations, CRP being elevated from days 1 to 12 p.i. and peaking at 10 times the day 0-levels on day 1 p.i. SAA rose quickly to peak levels of 30–40 times the day 0-level on days 1–2 and returned to pre-inoculation level on day 5 p.i. Hp and pig-MAP showed slightly slower responses, both peaking around 5 days p.i. Hp was increased throughout the experiment with maximum levels around 10 times the day 0-levels, and pig-MAP was elevated on days 1–12 p.i. with peak levels of around seven times the day 0-levels. Apo A-I was decreased from days 1 to 8 and showed minimum levels of about 40% of day 0-levels around 1–2 days p.i. No clear pattern of changes in albumin levels could be identified. One pig, showing clinical signs on day 2 only, also showed an APP response, although of a relatively short duration, whereas three pigs presenting clinical signs for several days had a more protracted acute phase response. Remarkably, the one pig showing no clinical signs and no arthritic lesions showed an APP response comparable to that of the other, clinically affected pigs. Thus, both acute clinical and subclinical S. suis infection could be revealed by the measurement of one or more of the APPs CRP, SAA, Hp, pig-MAP and Apo A-I. The combined measurement of two or three APPs, including proteins with slow and fast kinetics, should be used to achieve the highest sensitivity for the detection of ongoing S. suis infection during a prolonged time period. A diagnostic tool based on such APP-measurements could considerably improve strategic control procedures for this important infection.

Monitoring health by values of acute phase proteins

A systemic acute phase reaction may develop during infection and inflammation, due to the action of peripherally liberated proinflammatory cytokines. Hepatic metabolism changes, and negative and positive acute phase proteins (APPs) can be measured in the blood: the APPs therefore represent appropriate analytes to assess health. While they are non-specific markers, their levels change with biological effects and this can be used to assess nutritional deficits and reactive processes, especially when positive and negative acute phase variables are combined in an index. Unfortunately, at present, no comprehensive, easy-to-use and cheap system is available to assess various acute phase proteins in serum or blood samples. Protein micro-array technology may satisfy this need; it will permit simultaneous analysis of numerous analytes in the same small volume sample and enable integration of information derived from systemic reactivity and nutrition with disease-specific variables. Applying such technology may help to address health problems in many countries.