Acute phase protein response of ewes and the release of PGFM in relation to uterine involution and the presence of intrauterine bacteria.

The rate of uterine involution postpartum was monitored in 13 suckling mule ewes by using radio-opaque markers and radiography, and each ewe was also monitored for intrauterine bacterial contamination during the first week, using a sterile guarded swab. Peripheral plasma or serum concentrations of haptoglobin, seromucoid, ceruloplasmin and 15-keto-13,14-dihydro-prostaglandin F2 alpha (PGFM) were measured up to six weeks postpartum. The maximum reduction in the length of the uterine body and in the diameters of the horns occurred by 28 days postpartum, except in one ewe in which the size of the uterus continued to decrease for 42 days. Four ewes were positive for intrauterine bacterial contamination; Escherichia coli, clostridial species, Staphylococcus aureus, Streptococcus uberis and Enterococcus species were isolated in pure or mixed culture. The presence of intrauterine bacteria did not affect the time for the completion of uterine involution. No bacteria were isolated from the ewe in which involution was delayed, but it had a different acute phase protein response and was therefore excluded from further analyses. In the remaining 12 ewes the mean postpartum haptoglobin response increased, with peak concentrations occurring on day 1, and decreased slowly as uterine involution progressed, but the four contaminated ewes had a significantly greater response. There was no difference between the prepartum and postpartum concentrations of seromucoid in the eight sterile ewes, but significant increases were observed in the contaminated group; the concentrations of ceruloplasmin did not vary in either group. The concentrations of PGFM were higher during the early postpartum period in the ewes with contaminated uteri.     

Association between postpartum pyrexia and uterine bacterial infection in dairy cattle

The temperature of 90 dairy cattle was recorded for the first 10 days after parturition and the animals were categorised as either normal (< 39.7 degreesC) or pyrexic. Swabs were collected from the uterine lumen seven, 14, 21 and 28 days after parturition for aerobic and anaerobic culture; bacteria were identified and their growth was scored semiquantitatively. Blood samples were collected three times a week for the estimation of the concentrations of acute phase proteins. The cows' temperatures were often above the accepted normal range, but it was not a good indicator of the number of bacteria in the uterus. However, pyrexia was correlated with the presence of specific uterine pathogens (P < 0.05) and in particular with Prevotella species (P < 0.01). The pyrexic animals had a higher plasma concentration of the acute phase protein (alpha1-acid glycoprotein (P < 0.05). Although pyrexia is an indicator of postpartum inflammation, additional clinical signs are necessary to identify uterine bacterial infection.     

Association of bovine respiratory disease with clinical status and acute phase proteins in calves

Eighty-four calves with respiratory disease from 18 herds in different parts of Finland were chosen for a study evaluating the capacity of different respiratory pathogens to cause changes in different acute phase protein concentrations, white blood cell (WBC) count and clinical signs. The selected acute phase proteins were fibrinogen, haptoglobin, serum amyloid-A, lipopolysaccharide binding protein and alpha1-acid glycoprotein. From each calf, a paired blood sample was obtained for serological studies of bovine parainfluenza virus-3, bovine respiratory syncytial virus, bovine coronavirus, bovine adenovirus-3 and bovine adenovirus-7. Tracheobronchial lavage was performed to detect bacteria and mycoplasma. Isolation of Pasteurella multocida was associated with increased concentrations of all tested acute phase proteins. For other pathogens, no significant relationships were observed. No association was present between viral or bacterial findings and WBC count.     

Acute phase response and mastitis in the cow

The levels of three plasma proteins, which are classed as acute phase reactants, were compared in a group of cows which suffered from mastitis with those in a group of cows which were clinically normal. The plasma levels of haptoglobin, ceruloplasmin and alpha 1 antitrypsin were higher in the cows with mastitis than in normal cows.     

Acute phase proteins in grass sickness (equine dysautonomia)

Four acute phase proteins were assayed in the serum of normal horses and those with acute, subacute and chronic grass sickness, colic and inflammatory conditions, in order to investigate their diagnostic value in grass sickness. The grass sickness and inflammation group had a significantly increased haptoglobin concentration (P less than 0.01-P less than 0.001). Orosomucoid was elevated in acute, subacute and chronic grass sickness and inflammation (P less than 0.001, P less than 0.001, P less than 0.05 and P less than 0.05, respectively). Highest concentrations of haptoglobin and orosomucoid were recorded in subacute grass sickness. Ceruloplasmin was significantly higher in acute grass sickness cases than all other groups except the colic group (P less than 0.05-P less than 0.01). alpha 2-macroglobulin was significantly higher in acute grass sickness than normal, colic and chronic grass sickness cases (P less than 0.01, P less than 0.05 and P less than 0.05). The time scale of changes suggests that the stimulus to haptoglobin and orosomucoid synthesis occurs at the onset of clinical signs whereas the increase in ceruloplasmin and alpha 2-macroglobulin is more likely to reflect haemoconcentration.     

Effect of postpartum manual examination of the vagina on uterine bacterial contamination in cows

Twenty-one days after they had calved, the vaginas of 34 cows were examined with a clean gloved hand, and 26 cows were left unexamined. Swabs were collected from the lumen of the uterine body of the cows on the same day and seven days later; bacteria were identified by aerobic and anaerobic culture, and bacterial growth was scored semi-quantitatively. On the same days, blood samples were collected and the concentrations of acute phase proteins were measured, and the diameters of the cows' uterine horns were measured by transrectal ultrasonography. The vaginal examinations did not result in uterine bacterial contamination or an acute phase protein response, and they did not affect the diameters of the uterine horns.     

Comparison of two automated spectrophotometric methods for ceruloplasmin measurement in pigs

Ceruloplasmin (Cp) determination could provide an objective measure of the health status of an animal and could be used as marker of animal health and welfare (Skinner, 2001) (Skinner, J. G., 2001. Special report. International standardization of acute phase proteins. Veterinary Clinical Pathology 30, 2-7.) but only manual methods have been reported to determine Cp concentrations in pigs (McCosker, 1961; Toussaint et al., 1995; Eckersall et al., 1996) (McCosker, P. J., 1961. Paraphenylenediamine oxidase activity and copper-levels in mammalian plasmas. Nature. 190, 887-889; Toussaint, M. J. M., Van Ederen, A. M., Gruys, E., 1995. Implication of clinical pathology in assessment of animal health and in animal production and meat inspection. Comparative Haematology International 5, 149-157; Eckersall, P. D., Saini, P. K., McComb, C., 1996. The acute phase response of acid soluble glycoprotein, alpha(1)-acid glycoprotein, ceruloplasmin, haptoglobin and C-reactive protein, in the pig. Veterinary Immunology and Immunopathology 51, 377-385). In the present study two automated methods based on the use of two different substrates for the determination of serum ceruloplasmin in pigs were developed, evaluated and compared. Both methods showed a good precision and detection limits, with no signs of inaccuracy and could be applied to biochemical autoanalyzers usually found in clinical laboratories using only minimal amounts of serum. Additionally the behaviour of Cp in experimental and clinical situations was studied showing an increase of around two fold after turpentine administration and significantly higher values in cases of pigs with inflammatory conditions when compared with healthy pigs.     

Serum concentration of some acute phase proteins in naturally occurring canine babesiosis: a preliminary study

BACKGROUND: Serum concentrations of acute phase proteins can provide valuable diagnostic information in the detection, prognosis, or monitoring of disease. Information available on the acute phase response in naturally occurring canine babesiosis is limited. OBJECTIVE: The purpose of this investigation was to retrospectively evaluate serum concentrations of haptoglobin, C-reactive protein, and ceruloplasmin in dogs naturally infected with Babesia canis. METHODS: Haptoglobin, C-reactive protein, and ceruloplasmin concentrations were measured in serum samples from dogs with uncomplicated (n = 6) and complicated (n = 1) babesiosis and compared with 6 healthy dogs. RESULTS: Serum C-reactive protein and ceruloplasmin concentrations were significantly higher in dogs with babesiosis; however, serum haptoglobin concentration was significantly lower compared with control dogs (P <.01). CONCLUSIONS: Results of this study suggest that acute phase protein concentrations could be beneficial in the diagnosis and determination of the severity of babesiosis in dogs.     

Acute phase proteins in cattle: discrimination between acute and chronic inflammation.

Acute phase proteins such as serum amyloid A, haptoglobin, and alpha 1-acid glycoprotein have been identified as markers of inflammation in cattle because they are produced by the liver in response to pro-inflammatory cytokines. This study was designed to assess whether they could be used to discriminate between acute and chronic inflammation. Their concentrations were measured in serum samples from 81 cattle in which inflammation was classified by thorough clinical examination, supported by postmortem findings, as being acute in severity in 31 and chronic in 50. The classical haematological markers of inflammation were also determined in blood from the animals. Serum amyloid A had a maximum (100 per cent) clinical sensitivity in discriminating between the acute and chronic cases, and haptoglobin had the highest clinical specificity of 76 per cent; counts of neutrophils and band neutrophils had sensitivities of 71 per cent and 42 per cent and specificities of 30 per cent and 72 per cent, respectively. It was concluded that serum amyloid A and haptoglobin may be used to discriminate between acute and chronic inflammatory conditions.     

Regulation of bovine acute phase responses by recombinant interleukin-1 beta.

The acute phase response is a collection of physiologic changes initiated early in the inflammatory process. This response is comprised of both localized changes at the site of infection or injury and the initiation of systemic responses, such as the increase in production of acute phase proteins. Cytokines such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF) play key roles in the regulation of acute phase response in the species studied to date. To better characterize the acute phase response of cattle, recombinant bovine (rBo). IL-1 beta was administered to cattle. A single administration of rBoIL-1 beta was able to induce a dose dependent increase in body temperature, circulating leukocytes, and serum haptoglobin and fibrinogen concentrations, as well as a decrease in plasma zinc concentration. Five daily administrations of rBoIL-1 beta resulted in heightened and prolonged elevations of haptoglobin and fibrinogen. In addition, alpha 1-acid glycoprotein levels were increased, a response not seen after a single administration of rBoIL-1 beta. These results indicate that IL-1 is an important regulator of the acute phase response in cattle.     

Changes in concentrations of serum amyloid A protein, alpha 1-acid glycoprotein, haptoglobin, and C-reactive protein in feline sera due to induced inflammation and surgery

To identify candidates for feline acute phase proteins, the concentrations of serum amyloid A protein (SAA), alpha 1-acid glycoprotein (alpha 1-AG), C-reactive protein (CRP), and haptoglobin (Hp) were measured in sera isolated from clinically normal and hospitalized (or diseased) cats, from cats with experimentally induced inflammation, and cats subjected to surgery for urinary diversion. Measurements were made by sandwich enzyme-linked immunosorbent assay and single radial immunodiffusion. The concentrations of SAA, alpha 1-AG, and Hp in sera from hospitalized cats were 7-11 times higher than in clinically normal cats. Similar results were obtained for the concentrations of SAA, alpha 1-AG, and Hp in cats with induced inflammation and cats subjected to surgery. By contrast, the serum concentration of feline CRP did not change significantly between clinically normal cats and hospitalized cats or inflammation-induced or post-surgery cats. Feline SAA concentration was found to increase earliest, with alpha 1-AG and Hp beginning to increase thereafter. From these results, feline SAA is concluded to be an acute phase reactant at the early stage of inflammation.     

Diagnostic utility of measuring serum amyloid A with a latex agglutination turbidimetric immunoassay in bovine mastitis: Comparison with haptoglobin and alpha 1 acid glycoprotein

This study established the precision and accuracy of a modified latex agglutination turbidimetric immunoassay (LATIA) reagent, and evaluated the ability of the measurement of serum amyloid A (SAA) compared to haptoglobin and α1-acid glycoprotein, which are acute phase proteins (APPs), for diagnosis of clinical mastitis. Concentrations of APPs in cows with mastitis were significantly higher than those in healthy cow. Only the plasma SAA concentration in cows with clinical mastitis (44.90 mg/l; n=15) was significantly higher than that in those with subclinical mastitis (10.70 mg/l; n=16), enabling their diagnosis in contrast to other APPs. Thus, the SAA assay using a LATIA reagent is useful in assessing mastitis severity due to its higher sensitivity and specificity than other APP assays.     

The course of acute-phase proteins and serum cortisol in mastitis metritis agalactia (MMA) of the sow and sow performance

The objective of this study was to evaluate changes in acute-phase proteins (APPs) during mastitis metritis agalactia (MMA) in sows. Sows with MMA (group one, n=15) and healthy sows (group two, n = 15) were evaluated at days 0, 5, 10, 15, and 20 postpartum. Number of total born, liveborn, stillborn, and mummified pigs did not differ significantly between the groups. Preweaning mortality was higher (P < 0.001) among MMA sows than among healthy control animals. The offspring of healthy sows had higher (P < 0.05) weaning litter weights than the off-spring of MMA sows. Mean serum alpha 1-acid glycoprotein (AGP) concentrations were higher in MMA sows on the days 1 (P < 0.05), 5 (P = 0.05), and 10 (P < 0.001) post partum. Mean serum haptoglobin (HPT) was higher in MMA sows on days 1, 5 (P < 0.001), and 10 (P < 0.05) of lactation. Cortisol serum concentrations up to day 10 post partum were higher (P < 0.001) in MMA sows than in healthy sows. AGP was negatively correlated with litter weight, indicating that activation of the cellular immune response in sows negatively affects the growth rate of suckling piglets. Correlations were found between the overall means for weight, acute-phase proteins, and serum cortisol concentration.     

Physiological Concentrations of Acute-Phase Proteins and Immunoglobulins in Equine Synovial Fluid

Synovial fluid (SF) is capable of reflecting infectious, immunological, or inflammatory joint conditions in horses by altering its composition and appearance. Although plasma and SF compositions are quantitatively different, this latter compartment reflects changes in plasma macromolecules. Therefore, changes in serum immunoglobulin protein concentrations tend also to alter intracapsular levels. Therefore, it is necessary to know the physiological concentrations of proteins present in SF. The aim of this study was to determine the levels of total protein, albumin, transferrin, haptoglobin, α1-acid glycoprotein, ceruloplasmin, and immunoglobulins A and G in SF of six healthy horses. The synovial proteinogram was obtained by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The SF proteins reached a maximum of 25% of serum concentrations, varying inversely with molecular weight of the protein, except for the ceruloplasmin.     

Acute phase proteins in healthy and sick cats

Serum acute phase protein concentrations are used as diagnostic, therapeutic and prognostic markers in human and, less frequently, in animal medicine. The aim of this study was to determine how the health status and signalment of the cat are associated with concentrations of acute phase proteins. Generally, medians of the positive acute phase proteins appeared to be higher in sick cats compared to healthy cats. In multivariable regression models, log-transformed serum amyloid A concentration was higher in older cats, in sick and in female cats, while log-transformed α1-acid glycoprotein and haptoglobin concentrations were higher in older cats and were associated with interactions of health status (sick/healthy) and gender (male/female). The data from healthy cats in this study contribute to the limited knowledge of normal reference ranges for this species. This study highlights the potential of acute phase proteins as diagnostic markers in sick cats, but also emphasises that the signalment of the cat needs to be taken into consideration.     

Bovine acute phase response following turpentine injection

The serum levels of five proteins, alpha 1 antitrypsin, ceruloplasmin, fibrinogen, haptoglobin and seromucoid, were measured daily in calves after the subcutaneous injection of oil of turpentine. Raised concentrations were detected on the second and third days after injection with peak levels occurring on the fourth to seventh days and returning to normal by the 17th day. Levels of four of these proteins, alpha 1 antitrypsin, ceruloplasmin, haptoglobin and seromucoid were compared in the same calves following three different doses of turpentine. Levels of haptoglobin and seromucoid varied with the dose whereas ceruloplasmin and alpha 1 antitrypsin levels did not.     

Effect of transportation and commingling on the acute-phase protein response,growth, and feed intake of newly weaned beef calves

The objective of this study was to investigate the effect of transportation and commingling on measures of the acute-phase protein response in newly weaned beef calves. Thirty-two (Exp. 1; average BW = 266 +/- 20.8 kg) and thirty-six (Exp. 2; average BW = 222 +/- 34.6 kg) Brahman-crossbred calves were randomly allotted to one of four treatments (2 x 2 factorial arrangement [transportation x commingling] in a completely randomized design). Body weight and jugular blood were collected at weaning, after shipment, and 1, 3, and 7 d after transport for Exp. 1, and at weaning and 1, 5, 9, 13, 17, and 21 d after transport for Exp. 2. Feed intake within pen was recorded daily for Exp. 2. Plasma fibrinogen, ceruloplasmin, haptoglobin, and cortisol concentrations were determined for all collection times. Additionally, serum amyloid-A and alpha-acid glycoprotein concentrations were determined in Exp. 1 and 2, respectively. In Exp. 2, commingled calves tended (P = 0.13) to have a higher DMI than noncommingled calves (5.3 and 4.8 kg/d, respectively). Transported calves lost more BW than nontransported calves from the time of weaning to d 1 (2.0 and 3.1% more BW loss for Exp. 1 and 2, respectively). With the exception of haptoglobin in Exp. 1, each of the acute-phase proteins measured in these studies increased over each sampling day. In Exp. 1, transported calves had higher (P < 0.05) mean serum amyloid-A concentrations than nontransported calves (48.9 vs. 33.4 microg/mL). There was a significant sampling day x transportation interaction (P < 0.01) for fibrinogen, ceruloplasmin, and haptoglobin in Exp. 1; transported calves had higher concentrations of fibrinogen following transport and on d 2 and 3, and ceruloplasmin on d 3. Haptoglobin concentrations were higher (P = 0.04) in nontransported calves on d 1 and 2 of Exp. 1. In Exp. 2, overall mean haptoglobin concentrations were higher in nontransported vs. transported calves. The results of these studies indicate that stressors associated with transportation affect the acute-phase protein response in newly weaned beef calves. More research is needed to determine whether these proteins might be valuable indicators of stress following the weaning process.     

Changes in acute-phase proteins and cytokines in serum and milk whey from dairy cows with naturally occurring peracute mastitis caused by Klebsiella pneumoniae and the relationship to clinical outcome

This study was conducted to evaluate the changes in acute-phase proteins and cytokine concentrations in dairy cows with naturally occurring peracute Klebsiella pneumoniae (K. pneumoniae) mastitis and their association with the outcome of the disease. Seventeen Holstein cows with K. pneumoniae mastitis from 8 dairy farms were divided on the basis of outcome after local and systemic therapy into 2 groups comprising 8 euthanized cows and 9 that recovered. Changes in acute-phase proteins and cytokine concentrations in cows with K. pneumoniae mastitis were evaluated at the onset of the disease (day 0) and at days 3, 7 and 14 after therapy and compared with those of 13 healthy dairy cows. The concentrations of haptoglobin (Hp) and interleukin (IL)-6 in serum and α(1)-acid glycoprotein and IL-1β in serum and whey on day 0 were significantly (P<0.05) higher in the euthanized cows than in those that recovered and the healthy cows. A correlation (r=0.90, P<0.01, n=17) was found between IL-6 and Hp concentrations in sera from recovered and euthanized cows at day 0. This indicated that serum concentrations of Hp and IL-6 at the initial examination were prognostic factors for survival, and the cutoff values were 2,020 μg/ml and 32 ng/ml, respectively. These results suggest that IL-6 and Hp concentrations are involved in the manifestation of K. pneumoniae mastitis and may be possible indicators of the prognosis of peracute K. pneumoniae mastitis.     

Acute phase protein changes in calves during an outbreak of respiratory disease caused by bovine respiratory syncytial virus

Bovine acute phase proteins (APPs), lipopolysaccharide binding protein (LBP), serum amyloid A (SAA), haptoglobin (Hp) and alpha₁-acid glycoprotein (AGP) were evaluated as inflammatory markers during an outbreak of bovine respiratory disease (BRD) caused by bovine respiratory syncytial virus (BRSV). Calves (n = 10) presented mild to moderate signs of respiratory disease. Secondary bacterial infections, Pasteurella multocida and Mycoplasma dispar as major species, were detected in tracheobronchial lavage samples. Concentrations of SAA and LBP increased at week 1 had the highest values at week 3 and decreased at week 4 of outbreak. Some calves had high Hp concentrations at week 3, but AGP concentrations did not rise during respiratory disease. Higher SAA, LBP and Hp concentrations at a later stage of BRD (week 3) were associated with the low BRSV-specific IgG₁ production, suggesting that these calves had enhanced inflammatory response to the secondary bacterial infection. In conclusion, APPs (especially SAA and LBP) are sensitive markers of respiratory infection, and they may be useful to explore host response to the respiratory infections in clinical research.