The acute phase proteins (APP) are a group of blood proteins that contribute to restoring homeostasis and limiting microbial growth in an antibody-independent manner in animals subjected to infection, inflammation, surgical trauma or stress. In the last two decades, many advances have been made in monitoring APP in both farm and companion animals for clinical and experimental purposes. Also, the mechanism of the APP response is receiving attention in veterinary science in connection with the innate immune systems of animals. This review describes the results of recent research on animal APP, with special reference to their induction and regulatory mechanisms, their biological functions, and their current and future applications to veterinary diagnosis and animal production.

Current research on acute phase proteins in veterinary diagnosis: an overview.

The acute phase response is a complex systemic early-defense system activated by trauma, infection, stress, neoplasia, and inflammation. Although nonspecific, it serves as a core of the innate immune response involving physical and molecular barriers and responses that serve to prevent infection, clear potential pathogens, initiate inflammatory processes, and contribute to resolution and the healing process. Acute phase proteins, an integral part of the acute phase response, have been a focus of many applications in human diagnostic medicine and recently have been identified in common animal species. Potential applications to diagnosis, prognosis, assessment of animal health, and laboratory animal welfare are readily apparent.

Acute phase response in animals: a review.

Nematode Parasites of Vertebrates: Their Development and Transmission

The acute phase response is a nonspecific inflammatory reaction of the host that occurs shortly after any tissue injury. The response includes changes in the concentration of plasma proteins called acute phase proteins (APPs), some of which decrease in concentration (negative APPs), such as albumin or transferrin, and others of which increase in concentration (positive APPs), such as C-reactive protein, serum amyloid A, haptoglobin, alpha-1-acid glycoprotein, and ceruloplasmin. Most positive APPs are glycoproteins synthesized mainly by hepatocytes upon stimulation by proinflammatory cytokines and released into the bloodstream. The acute phase response and clinical application of monitoring APPs in dogs and cats are reviewed in this article, including biochemical characteristics, assays developed for each individual APP, and preanalytic and analytic factors influencing APP results that should be taken into account for proper and adequate clinical interpretation. In addition, the diagnostic use of APPs and their possible application in monitoring treatment, which can be considered one of the most interesting and promising practical applications of these proteins, will be discussed. Finally, challenges and future developments of APPs in dogs and cats will be considered, because it is expected that new and cheaper automated assays for determination of the main APPs in small animals will contribute to a wider use of these proteins as biomarkers of infection and inflammatory lesions.

Acute phase proteins in dogs and cats: current knowledge and future perspectives

Acute phase proteins (APPs) have been used as biomarkers of inflammation, infection and trauma for decades in human medicine but have been relatively under-utilised in the context of veterinary medicine. However, significant progress has been made in the detection, measurement and application of APPs as biomarkers in both companion and farm animal medicine over recent years. In the dog, C-reactive protein, haptoglobin and serum amyloid A have been identified as significant diagnostic 'markers' of steroid-responsive meningitis-arteritis, while in cats and cattle haptoglobin and alpha(1) acid glycoprotein and haptoglobin and serum amyloid A have proved valuable biomarkers of disease, respectively. In dairy cattle, haptoglobin and a mammary-associated serum amyloid A3 isoform, produced by the inflamed mammary gland during episodes of mastitis, have great potential as biomarkers of this economically important disease. Understanding the use of APP as biomarkers of inflammatory conditions of domestic animals has expanded significantly over recent years, and, with the insights provided by ongoing research, it is likely that these compounds will be increasingly used in the future in the diagnosis and prognosis of both companion and farm animal disease.

Acute phase proteins: Biomarkers of infection and inflammation in veterinary medicine

The aim of this review is to study the main spectrophotometric methods used to evaluate total antioxidant capacity (TAC) in serum samples of dogs. Total antioxidant capacity (TAC) is an analyte frequently used to assess the antioxidant status of biological samples and can evaluate the antioxidant response against the free radicals produced in a given disease. Trolox equivalent antioxidant capacity (TEAC), ferric reducing ability of plasma (FRAP), and cupric reducing antioxidant capacity (CUPRAC) are different assays described to determine TAC of a sample. This review explains the basis of each assay and their application in the determination of TAC in dogs, and also provides selected information about reports in humans for comparative purposes. It is concluded that, ideally, various different assays integrated in a panel should be used for TAC evaluation, since depending on the assay performed TAC results can be markedly different.

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Spectrophotometric assays for total antioxidant capacity (TAC) in dog serum: an update.

In recent decades there has been a growing concern about animal stress on intensive pig farms due to the undesirable consequences that stress produces in the normal physiology of pigs and its effects on their welfare and general productive performance. This review analyses the most important types of stress (social, environmental, metabolic, immunological and due to human handling), and their biological consequences for pigs. The physio-pathological changes associated with stress are described, as well as the negative effects of stress on pig production. In addition an update of the different biomarkers used for the evaluation of stress is provided. These biomarkers can be classified into four groups according to the physiological system or axis evaluated: sympathetic nervous system, hypothalamic-pituitary-adrenal axis, hypothalamic-pituitary-gonadal axis and immune system. Stress it is a process with multifactorial causes and produces an organic response that generates negative effects on animal health and production. Ideally, a panel of various biomarkers should be used to assess and evaluate the stress resulting from diverse causes and the different physiological systems involved in the stress response. We hope that this review will increase the understanding of the stress process, contribute to a better control and reduction of potential stressful stimuli in pigs and, finally, encourage future studies and developments to better monitor, detect and manage stress on pig farms.

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Causes, consequences and biomarkers of stress in swine: an update

The concentrations of haptoglobin, C-reactive protein and ceruloplasmin were measured in symptomatic and asymptomatic dogs naturally infected by Leishmania infantum, and in healthy uninfected dogs to determine the potential value of these proteins for the diagnosis and prognosis of leishmaniasis. The concentrations of the acute phase proteins were significantly higher in the dogs with leishmaniasis than in the control dogs, and the concentration of C-reactive protein was significantly higher in the symptomatic dogs than in the asymptomatic dogs. There were no correlations between the acute phase proteins and the gamma globulins, the albumin/globulin ratio or the titre of anti-leishmanial antibodies.

Serum concentrations of acute phase proteins in dogs with leishmaniasis

Five acute phase proteins (APPs) [C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), pig-MAP and albumin] were measured in pigs with naturally occurring infections by porcine reproductive and respiratory syndrome virus (PRRSV), Aujeszky's disease virus (ADV), porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae, and in animals with tail and ear bites, arthritis and other acute inflammatory processes. Healthy specific pathogen-free (SPF) pigs were used as controls. In PRRSV-infected pigs, all APPs with the exception of pig-MAP exhibited significant changes compared with controls. In animals affected with ADV only Hp presented changes of statistical significance, whereas pigs with PCV2 showed marked modifications in all APPs tested. Animals affected with Mycoplasmosis showed concentrations of all positive APPs significantly above levels obtained in SPF pigs, though albumin concentrations did not differ from controls. Finally, all APPs studied showed substantial changes in pigs with acute inflammation. The results indicated that an acute phase response was developed in the different diseases studied, this response being higher in animals with clinical signs and concurrent bacterial processes. Haptoglobin would be the APP that better reflects pathological states; however, to get more complete and valuable information it might be advisable to perform APPs profiles including another APP, such as CRP or SAA.

Silvia Martínez-Subiela

Papers

Acute phase proteins in dogs and cats: current knowledge and future perspectives

Spectrophotometric assays for total antioxidant capacity (TAC) in dog serum: an update.

Causes, consequences and biomarkers of stress in swine: an update

Serum concentrations of acute phase proteins in dogs with leishmaniasis

Porcine acute phase protein concentrations in different diseases in field conditions.