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      The Evidence for a Causal Link Between Disease and Damaging Behavior in Pigs

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          Abstract

          Damaging behaviors (DB) such as tail and ear biting are prevalent in pig production and reduce welfare and performance. Anecdotal reports suggest that health challenges increase the risk of tail-biting. The prevalence of tail damage and health problems show high correlations across batches within and between farms. There are many common risk factors for tail-biting and health problems, notably respiratory, enteric and locomotory diseases. These include suboptimal thermal climate, hygiene, stocking density and feed quality. The prevalence of tail damage and health problems also show high correlations across batches within and between farms. However, limited evidence supports two likely causal mechanisms for a direct link between DB and health problems. The first is that generalized poor health (e.g., enzootic pneumonia) on farm poses an increased risk of pigs performing DB. Recent studies indicate a possible causal link between an experimental inflammation and an increase in DB, and suggest a link between cytokines and tail-biting. The negative effects of poor health on the ingestion and processing of nutrients means that immune-stimulated pigs may develop specific nutrient deficiencies, increasing DB. The second causal mechanism involves tail-biting causing poor health. Indirectly, pathogens enter the body via the tail lesion and once infected, systemic spread of infection may occur. This occurs mainly via the venous route targeting the lungs, and to a lesser extent via cerebrospinal fluid and the lymphatic system. In carcasses with tail lesions, there is an increase in lung lesions, abscessation, arthritis and osteomyelitis. There is also evidence for the direct spread of pathogens between biters and victims. In summary, the literature supports the association between poor health and DB, particularly tail-biting. However, there is insufficient evidence to confirm causality in either direction. Nevertheless, the limited evidence is compelling enough to suggest that improvements to management and housing to enhance pig health will reduce DB. In the same way, improvements to housing and management designed to address DB, are likely to result in benefits to pig health. While most of the available literature relates to tail-biting, we suggest that similar mechanisms are responsible for links between health and other DB.

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          From inflammation to sickness and depression: when the immune system subjugates the brain.

          In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.
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            The macrophage theory of depression.

            R.S. Smith (1991)
            Excessive secretion of macrophage monokines is proposed as the cause of depression. Monokines when given to volunteers can produce the symptoms necessary for the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised (DSM-III-R) diagnosis of major depressive episode. Interleukin-1 (IL-1) can provoke the hormone abnormalities linked with depression. This theory provides an explanation for the significant association of depression with coronary heart disease, rheumatoid arthritis, stroke and other diseases where macrophage activation occurs. The 3:1 female/male incidence of depression ratio is accounted for by estrogen's ability to activate macrophages. The extraordinary low rate of depression in Japan is consistent with the suppressive effect of eicosapentanoic acid on macrophages. Fish oil is proposed as a prophylaxis against depression and omega-6 fat as a promoter. Infection, tissue damage, respiratory allergies and antigens found in food are some of the possible causes of macrophage activation triggering depression.
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              Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice.

              Although elevated activity of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) has been proposed to mediate comorbid depression in inflammatory disorders, its causative role has never been tested. We report that peripheral administration of lipopolysaccharide (LPS) activates IDO and culminates in a distinct depressive-like behavioral syndrome, measured by increased duration of immobility in both the forced-swim and tail suspension tests. Blockade of IDO activation either indirectly with the anti-inflammatory tetracycline derivative minocycline, that attenuates LPS-induced expression of proinflammatory cytokines, or directly with the IDO antagonist 1-methyltryptophan (1-MT), prevents development of depressive-like behavior. Both minocycline and 1-MT normalize the kynurenine/tryptophan ratio in the plasma and brain of LPS-treated mice without changing the LPS-induced increase in turnover of brain serotonin. Administration of L-kynurenine, a metabolite of tryptophan that is generated by IDO, to naive mice dose dependently induces depressive-like behavior. These results implicate IDO as a critical molecular mediator of inflammation-induced depressive-like behavior, probably through the catabolism of tryptophan along the kynurenine pathway.
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                Author and article information

                Contributors
                Journal
                Front Vet Sci
                Front Vet Sci
                Front. Vet. Sci.
                Frontiers in Veterinary Science
                Frontiers Media S.A.
                2297-1769
                27 January 2022
                2021
                : 8
                : 771682
                Affiliations
                [1] 1Teagasc Animal and Grassland Research and Innovation Centre , Cork, Ireland
                [2] 2School of Natural and Environmental Sciences, Newcastle University , Newcastle upon Tyne, United Kingdom
                [3] 3Adaptation Physiology Group, Department of Animal Sciences, Wageningen University & Research , Wageningen, Netherlands
                [4] 4ONIRIS , Nantes, France
                [5] 5Biotechnical Faculty, Department of Animal Science, University of Ljubljana , Ljubljana, Slovenia
                [6] 6Chamber of Agriculture of North Rhine-Westphalia, Animal Health Services , Bad Sassendorf, Germany
                [7] 7Faculty of Veterinary Medicine, Department of Paraclinical Sciences, Norwegian University of Life Sciences , Oslo, Norway
                [8] 8Faculty of Veterinary Medicine, Trakia University , Stara Zagora, Bulgaria
                [9] 9Ellinikos Georgikos Organismos-DIMITRA (ELGO-DIMITRA), Veterinary Research Institute , Thessaloniki, Greece
                [10] 10Department of Production Animal Medicine, Research Centre for Animal Welfare, University of Helsinki , Helsinki, Finland
                Author notes

                Edited by: Marian Stamp Dawkins, University of Oxford, United Kingdom

                Reviewed by: Suzanne D. E. Held, University of Bristol, United Kingdom; Irene Camerlink, Polish Academy of Sciences (PAS), Poland

                *Correspondence: Laura A. Boyle laura.boyle@ 123456teagasc.ie

                This article was submitted to Animal Behavior and Welfare, a section of the journal Frontiers in Veterinary Science

                Article
                10.3389/fvets.2021.771682
                8828939
                35155642
                2e90cbe5-0780-49e7-bfb9-3ffc85f5f49a
                Copyright © 2022 Boyle, Edwards, Bolhuis, Pol, Šemrov, Schütze, Nordgreen, Bozakova, Sossidou and Valros.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 06 September 2021
                : 06 December 2021
                Page count
                Figures: 0, Tables: 2, Equations: 0, References: 339, Pages: 28, Words: 24722
                Funding
                Funded by: Teagasc, doi 10.13039/501100001604;
                Categories
                Veterinary Science
                Review

                welfare,health,lesion,risk,behavior,pig,tail biting
                welfare, health, lesion, risk, behavior, pig, tail biting

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