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Front Vet Sci. 2021 Jan 07;7:617634. doi: 10.3389/fvets.2020.617634. eCollection 2020.

The Effect of LPS and Ketoprofen on Cytokines, Brain Monoamines, and Social Behavior in Group-Housed Pigs.

Frontiers in veterinary science

Christina Veit, Andrew M Janczak, Birgit Ranheim, Judit Vas, Anna Valros, Dale A Sandercock, Petteri Piepponen, Daniela Dulgheriu, Janicke Nordgreen

Affiliations

  1. Department of Paraclinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, Norway.
  2. Department of Production Animal Clinical Science, Faculty of Veterinary Medicine, Norwegian University of Life Sciences, Oslo, Norway.
  3. Department of Animal and Aquacultural Sciences, Faculty of Biosciences, Norwegian University of Life Sciences, Ås, Norway.
  4. Research Centre for Animal Welfare, Department of Production Animal Medicine, University of Helsinki, Helsinki, Finland.
  5. Animal and Veterinary Science Research Group, Scotland's Rural College, Roslin Institute Building, Easter Bush, Midlothian, United Kingdom.
  6. Division of Pharmacology and Pharmacotherapy, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.

PMID: 33585605 PMCID: PMC7873924 DOI: 10.3389/fvets.2020.617634

Abstract

Poor health is a risk factor for damaging behaviors, but the mechanisms behind this link are unknown. Injection of pigs with lipopolysaccharide (LPS) can be used to model aspects of poor health. Recent studies have shown that LPS-injected pigs perform more tail- and ear-directed behavior compared to saline-injected pigs and suggest that pro-inflammatory cytokines may play a role in these behaviors. The aims of this study were to test the effect of LPS on the social behavior of pigs and the neurotransmitters and modulators in their brains and to test the effect of a nonsteroidal anti-inflammatory drug on the effects of LPS. Fifty-two female pigs (11-12 weeks) were allocated to four treatments comprising two injections: saline-saline (SS), saline-LPS (SL), ketoprofen-saline (KS), and ketoprofen-LPS (KL). Activity was scan-sampled every 5 min for 6 h after the last injection in the pen. Social behavior was observed continuously in 10 × 15-min bouts between 8 a.m. and 5 p.m. 1 day before (baseline) and 1 and 2 days after the injection. Saliva was analyzed for cortisol and plasma for tryptophan and kynurenine. The frontal cortex, hippocampus, hypothalamus, and brain stem were sampled 72 h after the injection and analyzed for cytokines and monoamines. LPS activated the HPA axis and decreased the activity within 6 h after the injection. Ketoprofen lowered the effect of LPS on cortisol release and attenuated the behavioral signs of sickness in challenged pigs. SL pigs manipulated the ears of their pen mates significantly longer than SS pigs 2 days after the injection. LPS had no observed effect on IFN-γ, TNF-α, and IL-18. At 72 h after the injection, plasma tryptophan was depleted in SL pigs, and tryptophan and kynurenine concentrations in the frontal cortex and brain stem of SL pigs were significantly lower compared to those in SS pigs. Dopamine concentrations in the hypothalamus of SL pigs were significantly lower compared to those in SS pigs. Serotonin concentrations in the hypothalamus and noradrenaline concentrations in the hippocampus of SL pigs were significantly lower compared to those in KL pigs. In conclusion, LPS influenced the different neurotransmitters and modulators in the brain that are hypothesized to play an important role in the regulation of mood and behavior.

Copyright © 2021 Veit, Janczak, Ranheim, Vas, Valros, Sandercock, Piepponen, Dulgheriu and Nordgreen.

Keywords: cytokines; ketoprofen; kynurenine; lipopolysaccharide (LPS); monoamines; sickness behavior; social behavior; tryptophan

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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