The acute phase proteins response belongs to the innate defence mechanism. When an animal is challenged by infections, injuries, inflammatory lesions, or stress, profound physiological, metabolic and endocrine changes are triggered. These alterations in homeostasis are collectively known as an acute phase response, and include an increase in the circulating concentration of some blood proteins: the so-called acute phase proteins (APP). There are different classes of APP depending on the magnitude of the change in concentration they can experience. Moreover, the APP pattern depends on the species.

The APP are a heterogeneous group of proteins with different roles, all considered important to overcome the period that follows the challenge. APP fulfil multiple functions, from acting in the first line of defence (fight against pathogens, neutralization of harmful molecules) to participating in the regulation of many of the mechanisms triggered during the acute phase response. From a diagnostic point of view APP are of interest because they can be measured to detect all kind of situations causing an inflammatory response (an acute phase response) and therefore they can be used as general biomarkers for animal health and welfare.

 

Acute Phase Proteins in different species

 Major
(Increase > 10 times)
Moderate
(Increase 2-5 times)
Negative
(Decrease)
Pig CRP, SAA
pig-MAP/ITIH4
Haptoglobin
Ceruloplasmin Albumin
ApoA-I
Cattle Haptoglobin
SAA, ITIH4
α1-acid glycoprotein Albumin
ApoA-I
Dog CRP, SAA Haptoglobin, ITIH4,
α1-acid glycoprotein
Albumin

CRP: C-reactive protein, SAA: Serum Amyloid A, MAP: Major Acute phase protein, ITIH4: heavy chain 4 of the inter-alpha trypsin inhibitor family.

The Acute Phase Response

The Acute Phase Response

Main mechanisms triggered during an Acute Phase Response. The acute phase response is regulated by pro-inflammatory cytokines, which act as messengers between the lesion site and the different organs that take part in the response.

 

Acute phase proteins in pigs

Acute phase proteins in pigs

Acute phase proteins in pig production

APP can provide, by means of a single analysis, an overview of the animal health and welfare status at the farm. APP measurements can be used in the detection of subclinical diseases or stress-causing factors compromising animal welfare and reducing productive performance at the farm.

Use of APP at the farm

  • Detection of stress conditions or subclinical diseases
  • Measurement of the efficiency of the production system
  • Evaluate the health status of farms or animals
  • Incorporation into integrated quality assurance schemes

 

Use of APP at the farm

 

Acute phase proteins in experimental trials

APP measurements are useful in experimental trials aimed to evaluate veterinary medicines or other products related to animal health and welfare and affecting the inflammatory response (e.g. antibiotic, vaccines or vaccination programmes, anti-inflammatory drugs, probiotics, feed additives with anti-inflammatory properties, etc).

The analysis of APP is useful not only to compare experimental groups during the trial, but also before the start of the trial to detect pre-existing inflammatory processes that could bias the results.

Applications of APP in trials with experimental animals

  • Quantification of the inflammatory response in trials for evaluation of drugs
  • Experimental trials for the evaluation of rearing systems or products with an effect on animal health and welfare
  • Detection of systemic inflammation in toxicological studies (pre-clinical studies)
  • Normalization of the experimental trials with animals for experimentation, in order to avoid unnecessary repetitions (detection of inflammatory processes prior to the trial)
  • End point criterion to avoid unnecessary suffering of animals

 

Acute phase proteins in dogs

Acute phase proteins in dogs

C-reactive protein in the dog

In dogs, as in humans, the serum concentration of C-reactive protein (CRP) is very low in healthy individuals (few mg/L) but increases rapidly after inflammatory stimuli. CRP is used in the diagnosis and monitoring of inflammatory or infectious diseases. CRP levels have prognosis value as they reflect the evolution of a disease. The decrease in the CRP levels indicates recovery, whereas the persistence of elevated levels means that the inflammatory response is not adequately resolved. APP measurements are very useful to evaluate the efficacy of treatments, and to detect complications in a post-surgery follow up.

The fast response to inflammatory stimuli and its relatively short life make CRP an ideal test to determine the clinical situation of an animal at the time of taking the sample. CRP has higher diagnostic sensitivity than other unspecific markers of inflammation such as the albumin/globulin ratio or the WBC or neutrophil counts. Moreover, acute phase proteins are valuable for detection of inflammation in animals in which the bone marrow can not respond normally to the inflammatory stimulus, such as animals affected by leukemia or receiving chemotherapy.

Clinical use of CRP

  • Diagnostic and monitoring of inflammatory and infectious diseases
  • Evaluation of the efficacy of antibiotic treatment
  • Post surgery follow-up (detection of complications)

C-reactive protein in the dog

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