Acute phase response in reindeer after challenge with Escherichia coli endotoxin

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Abstract

The serum concentrations of two acute phase proteins (APPs), haptoglobin (Hp) and serum amyloid-A (SAA), were monitored in reindeer after challenge with endotoxin. Four adult female reindeer received either 0.1 μg/kg Escherichia coli 0111:B4 lipopolysaccharide B or saline solution intravenously. At the second challenge, the treatments were reversed. In addition to the APPs, changes in blood chemistry and rectal temperature were monitored. The endotoxin challenge caused a significant increase in SAA (peak 48 h) and a sharp decrease (8–12 h) of serum iron concentrations in all animals. The mean Hp concentration increased at 8 h and remained elevated until 48 h, but no statistically significant differences were found. This investigation demonstrates that challenge with a single-bolus dose of E. coli endotoxin can activate the acute phase response (APR) and SAA appears to be a more sensitive indicator of the APR than Hp during bacterial infection in reindeer.

Résumé

Les concentrations de deux protéines de l'inflammation, l'haptoglobine (Hp) et l'amyloı̈de A sérique (SAA), la température rectale et les paramètres biochimiques sanguins ont été suivis chez quatre rennes adultes femelles ayant reçu lors d'une première inoculation intraveineuse soit 0.1 μg/kg de lipopolysaccharide B d'Escherichia coli O111:B4, soit du sérum physiologique, puis lors d'une seconde inoculation l'inverse.

L'injection d'endotoxine a entraı̂né une augmentation significative de la concentration de SAA (pic à 48 h) et une diminution brutale (8–12 h) du fer sérique chez tous les animaux. La concentration moyenne d'Hp a augmenté à 8 h et est restée élevée jusqu'à 48 h, mais sans qu'aucune différence statistiquement significative ne soit trouvée. Ceci démontre qu'une inoculation unique d'endotoxine d'E. coli peut déclencher une réaction inflammatoire chez le renne et qu'en cas d'infection bactérienne la SAA apparaı̂t être plus sensible que l'Hp pour détecter cette réaction.

Introduction

The inflammatory reaction is a series of complex physiological events occurring in the host after tissue injury or infection. The purposes of these events are to eliminate the infecting agent, prevent further tissue damage and restore the homeostasis of the host organism. The early sets of reactions that occur immediately after tissue damage are known as the acute phase response (APR). It is characterized by the presence of an inflammatory reaction at the site of injury or infection and systemically by multiple changes throughout the organism such as fever, depression, leucocytosis, increased permeability of blood vessels, stimulation of adrenocorticotropic hormone (ACTH) production, redistribution of trace elements, etc. One of the main changes occurring during the APR is hepatic production of various plasma proteins [1]. These so-called acute phase proteins (APPs) play a very important role in the defense response of the host. For example, some APPs are involved in nonspecific protection against infections caused by gram-negative bacteria [2], but in many cases their exact physiological function is not clear.

Monitoring the plasma concentrations of APPs can provide information on progression of the APR. Their potential use in veterinary medicine has been extensively investigated and they are already widely used as markers of disease in veterinary and medical science. Some of the many applications for APPs include evaluation of collective health of herds by detection of subclinical diseases and identification of animals with inflammatory lesions at slaughter. Thus, APPs may also serve as valuable tools in reindeer husbandry as well as in giving diagnostic information on the detection, prognosis and monitoring of diseases in reindeer.

Although the APR is highly conserved in nature, APP profiles show significant variability between different species [3]. Haptoglobin (Hp) has been the APP most commonly monitored as a marker for inflammation [4], [5], [6], [7], [8] in cattle and other domestic ruminants. The plasma Hp concentration is very low in healthy bovines [7] but during the APR it can increase over 100-fold. Serum amyloid-A (SAA) is another major APP in many animal species, including cattle, and has been shown to be a good diagnostic marker for determining the presence of infections and inflammatory conditions [7], [9], [10], [11]. Evaluation of the concentrations of different APPs allows better estimates of the complex systemic effects of inflammatory mediators during various inflammatory conditions, e.g. in distinguishing between acute and chronic inflammation and for evaluation of disease severity.

The main objective here was to investigate the host response of reindeer (Rangifer tarandus tarandus) after bacterial endotoxin challenge as an acute phase stimulant and to evaluate the changes occurring in serum concentrations of SAA and Hp as potential markers of infections. In addition to the APPs, other changes occurring in blood chemistry and in some clinical parameters were also monitored.

Section snippets

Animals and experimental procedures

This experiment was carried out at the Zoological Gardens of the Department of Biology, University of Oulu, Finland. The first experiment was initiated on February 18, 2002 and the second on April 8, 2002. Eight adult female reindeer were randomly divided into two equal groups. The mean weight of the animals was 76.7 kg (range 67.5–90.5 kg) and age was 5 years (3–6 years). The groups were kept in two separate corrals (about 650 m2 each) in which they underwent a long adaptation period before

Results

After laboratory analysis, two reindeer were excluded from statistical analysis, one from each group. One reindeer already showed increased Hp (over 3-fold) and SAA (over 10-fold) concentrations in the 0-h sample, which remained high during the first experiment. Clear arthritic changes were found in the left tarsal joint of this animal at autopsy; in all other reindeer no pathological changes were found. The second excluded reindeer reacted very strongly to the restraint procedures used at the

Discussion

Bacterial endotoxins, which are LPSs from the cell wall of gram-negative bacteria, are considered to cause most pathophysiological reactions during bacterial infections. The physiological effects of LPS are based predominantly on activation of various molecular mediators [25] such as the cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6, which are released in response to LPS predominantly by monocytes and macrophages [26]. These inflammatory mediators initiate host

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