Acute phase proteins as local biomarkers of respiratory infection in calves

Abstract

BackgroundCumulating reports suggest that acute phase proteins (APPs) do not only play a role as systemic inflammatory mediators, but are also expressed in different tissues as local reaction to inflammatory stimuli. The present study aimed to evaluate presence and changes in luminal lung concentrations of the APPs haptoglobin (Hp), lipopolysaccharide binding protein (LBP), C-reactive protein (CRP), and lactoferrin (Lf) in calves with an acute respiratory disease experimentally induced by Chlamydia (C.) psittaci.ResultsIntra-bronchial inoculation of the pathogen resulted in a consistent respiratory illness. In venous blood of the infected calves (n = 13), concentrations of plasma proteins and serum LBP were assessed (i) before exposure and (ii) 8 times within 14 days after inoculation (dpi). Increasing clinical illness correlated significantly with increasing LBP—and decreasing albumin concentrations in blood, both verifying a systemic acute phase response.Broncho-alveolar lavage fluid (BALF) was obtained from all 13 calves experimentally infected with C. psittaci at 4, 9 and 14 dpi, and from 6 uninfected healthy calves. Concentrations of bovine serum albumin (BSA), Hp, LBP, CRP and Lf in BALF were determined by ELISA. In infected animals, absolute concentrations of LBP and Hp in BALF correlated significantly with the respiratory score. The quotient [LBP]/[BSA] in BALF peaked significantly in acutely infected animals (4 dpi), showed a time-dependent decrease during the recovery phase (9-14 dpi), and was significantly higher compared to healthy controls. Concentrations of Hp and Lf in BALF as well as [Hp]/[BSA]—and [Lf]/[BSA]-quotients decreased during the study in infected animals, but were never higher than in healthy controls. CRP concentrations and [CRP]/[BSA]-quotient did not express significant differences between infected and healthy animals or during the course of infection.ConclusionIn conclusion, absolute concentrations of LBP in blood and BALF as well as the quotient [LBP]/[BSA] in BALF perfectly paralleled the clinical course of respiratory illness after infection. Beside LBP, the suitability of Hp and Lf as local biomarkers of respiratory infections in cattle and their role in the local response to pathogens is worth further investigation, while CRP does not seem to play a role in local defense mechanisms of the bovine lung.

Acute phase proteins as promising biomarkers: Perspectives and limitations for human and veterinary medicine

“…Despite the long‐lasting application of APPs as common but nonspecific diagnostic and prognostic parameters, some distinct sets of APPs have recently been proposed as specific biomarkers, particularly with proteomic and glycoproteomic searches in body fluids. This has also been reflected in our studies with respect to a broad range of diseases like sepsis or acute respiratory infection , congenital or acquired nephropathies , and psoriasis . Unfortunately, many of these results were neglected by the scientific community and considered as not being of value of the low specificity of acute phase reactants in many diseases, sometimes by the discoverers themselves.…”

“…Similar findings have been reported for calves infected with Chlamydia psittaci . Again, in BALF, the significant rise in LBP, in particular, was much more meaningful than changes in lactoferrin (Lf) and Hpt .…”

“…This could explain why the concentration of Hpt in milk increases several hours earlier than in the blood . Moreover, Hpt is also released into bronchial fluid in respiratory infections and into the saliva of pigs and cattle . Hpt in the saliva of healthy pigs and humans exhibits a circadian pattern with higher concentrations in the morning.…”

Acute phase response in lame crossbred dairy cattle

“…Acute phase proteins (APPs) are the blood proteins that change in concentration in response to various inflammatory as well as non-inflammatory conditions in animals [1-7]. APPs are released from the liver after activation of hepatocytes by the proinflammatory cytokines (interleukin 1 [IL-1], IL-6, and tumor necrosis factor-α) which are secreted by the monocytes in response to bacterial toxins or tissue injury.…”

Evaluation of Acute Phase Proteins in Clinically Healthy Dairy Cows in Perinatal Period and During Lactation

“…mastitis or metritis, but also e.g. respiratory infections (Burfeind et al 2014, Prohl et al 2015. Haptoglobin is binding free haemoglobin in the blood plasma released from erythrocytes.…”