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A glucocorticoid receptor agonist improves post-weaning growth performance in segregated early-weaned pigs

  • H. Wooten (a1), J. J. McGlone (a1), M. Wachtel (a2), G. Thompson (a3), A. R. Rakhshandeh (a4) and A. Rakhshandeh (a1)...


While beneficial for sow reproductive efficiency and biosecurity, segregated early weaning (SEW) leads to a systemic immune response that adversely affects the digestive physiology and post-weaning growth of pigs. Two experiments were conducted to evaluate the effects of a glucocorticoid receptor agonist (GA) on growth performance, measures of immune function and intestinal integrity of SEW pigs. In both experiments, pigs were fed corn-soybean meal-based starter diets. In the first experiment, 48 pigs (initial BW 4.8 ± 0.7 kg) were weaned at 21 ± 1 days and randomly assigned to three GA treatment groups: 0, 0.2 and 0.6 mg GA/kg of BW injected intramuscularly. Treatments were administered one day before weaning. Pigs in the 0 mg GA group received sterile saline in place of GA. Body weight was measured daily from one day before to 7 days post-weaning, and then weekly until 28 days post-weaning. Piglets treated with 0.2 mg GA had a higher BW than piglets in other treatment groups during the 28-day course of the study (P <0.02). To further explore the mechanisms behind this result, a second experiment was performed in which a total of 18 gilts (BW 5.6 ± 0.85 kg) were randomly assigned into three treatment groups: suckling plus saline (UWS), weaned treated with GA (WGA; 0.2 mg GA/kg BW) and weaned plus saline (CON). Treatments were administered one day before and 3 days post-weaning. The WGA and CON groups were weaned at 23 ± 2 days, while the UWS group remained with sow for the duration of the study. Body weight was measured daily and blood plasma was collected at 0, 1, 4 and 5 days post-weaning. All gilts were euthanized 5 days after weaning and jejunum samples were collected for mucosal scrapings, histomorphological analysis and gene expression analysis. Plasma levels of interleukin-1β (IL-1β) and haptoglobin were lower in WGA pigs compared with CON (P <0.02), while plasma total antioxidant capacity was higher in WGA pigs compared with both CON and UWS groups (P <0.01). Relative to CON, GA downregulated IL-18 gene expression in the jejunum, as assessed by both tissue homogenate and mucosal scrapings, but it upregulated claudin-IV gene expression only in the tissue homogenate (P <0.01). These results suggest that GA treatment improves the growth performance of SEW pigs in part by mitigating the negative effects of systemic inflammation. However, the effect of GA on barrier integrity requires further investigation.


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Present address: 1308 Indiana Avenue, Lubbock, Texas 79409, USA



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Boivin, MA, Ye, D, Kennedy, JC, Al-Sadi, R, Shepela, C and Ma, TY 2006. Mechanism of glucocorticoid regulation of the intestinal tight junction barrier. AJP: Gastrointestinal and Liver Physiology 292, G590G598.
Campbell, JM, Crenshaw, JD and Polo, J 2013. The biological stress of early weaned piglets. Journal of Animal Science and Biotechnology 4, 25.
Cole, M a., Kim, PJ, Kalman, BA and Spencer, RL 2000. Dexamethasone suppression of corticosteroid secretion: Evaluation of the site of action by receptor measures and functional studies. Psychoneuroendocrinology 25, 151167.
Coutinho, AE and Chapman, KE 2011. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Molecular and Cellular Endocrinology 335, 213.
Cross, KP, Paul, RI and Goldman, RD 2011. Single-dose dexamethasone for mild-to-moderate asthma exacerbations: Effective, easy, and acceptable. Canadian Family Physician 57, 11341136.
de Kruijf, JM and Welling, AA 1988. Incidence of chronic inflammation in gilts and castrated boars. Tijdschrift voor Diergeneeskunde 113, 415417.
Désautés, C, Sarrieau, A, Caritez, JC and Mormède, P 1999. Behavior and pituitary-adrenal function in Large White and Meishan pigs. Domestic Animal Endocrinology 16, 193205.
Dionissopoulos, L, Dewey, CE, Namkung, H and De Lange, CFM 2006. Interleukin-1ra increases growth performance and body protein accretion and decreases the cytokine response in a model of subclinical disease in growing pigs. Animal Science 82, 509515.
Gabert, VM, Jorgensen, H and Nyachoti, CM 2000. Bioavailability of amino acids in feedstuffs for swine. In Swine Nutrition (ed. AJ Lewis and LL Southern), pp. 151186. CRC Press, Boca Raton, FL, USA.
Gatnau, R, Zimmerman, DR, Nissen, SL, Wannemuehler, M and Ewan, RC 1995. Effects of excess dietary leucine and leucine catabolites on growth and immune responses in weanling pigs. Journal of Animal Science 73, 159165.
Gómez, S, Angeles, ML and Cuáron, JA 1997. Growth performance and enzyme development in weanling pigs injected with dexamethasone. Journal of Animal Science 75, 9931000.
Hand, TW 2015. Interleukin-18: The bouncer at the mucosal bar. Cell 163, 13101312.
Handa, RJ and Weiser, MJ 2013. Gonadal steroid hormones and the hypothalamo-pituitary-adrenal axis. Frontiers in Neuroendocrinology 35, 197220.
Hu, CH, Xiao, K, Luan, ZS and Song, J 2013. Early weaning increases intestinal permeability, alters expression of cytokine and tight junction proteins, and activates mitogen-activated protein kinases in pigs. Journal of Animal Science 91, 10941101.
Ingram, DL and Dauncey, MJ 1985. Circadian rhythms in the pig. Comparative Biochemistry and Physiology 82, 15.
Karaki, S ichiro, Kaji, I, Otomo, Y, Tazoe, H and Kuwahara, A 2007. The tight junction component protein, claudin-4, is expressed by enteric neurons in the rat distal colon. Neuroscience Letters 428, 8892.
Kojima, CJ, Kattesh, HG, Roberts, MP and Sun, T 2008. Physiological and immunological responses to weaning and transport in the young pig: Modulation by administration of porcine somatotropin. Journal of Animal Science 86, 29132919.
Konsman, JP, Parnet, P and Dantzer, R 2002. Cytokine-induced sickness behaviour: Mechanisms and implications. Trends in Neurosciences 25, 154159.
Leppkes, M, Roulis, M, Neurath, MF, Kollias, G and Becker, C 2014. Pleiotropic functions of TNF-α in the regulation of the intestinal epithelial response to inflammation. International Immunology 26, 509515.
Livak, KJ and Schmittgen, TD 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 25, 402408.
Llamas Moya, S, Boyle, LA, Lynch, PB and Arkins, S 2008. Surgical castration of pigs affects the behavioural response to a low-dose lipopolysaccharide (LPS) challenge after weaning. Applied Animal Behaviour Science 112, 4057.
Margolis, KG and Gershon, MD 2016. Enteric neuronal regulation of intestinal inflammation. Trends in Neurosciences 39, 614624.
Conrad, MS, Sutton, BP, Larsen, R, Van Alstine, W G and Johnson, RW 2015. Early postnatal respiratory viral infection induces structural and neurochemical changes in the neonatal piglet brain. Brain, Behavior, and Immunity 48, 326335.
Medzhitov, R, Schneider, DS and Soares, MP 2012. Disease tolerance as a defense strategy. Science 335, 936941.
Miguel, JC, Chen, J, Van Alstine, WG and Johnson, RW 2010. Expression of inflammatory cytokines and toll-like receptors in the brain and respiratory tract of pigs infected with porcine reproductive and respiratory syndrome virus. Veterinary Immunology and Immunopathology 135, 314319.
Mittal, M, Siddiqui, MR, Tran, K, Reddy, SP and Malik, AB 2014. Reactive oxygen species in inflammation and tissue injury. Antioxidants & Redox Signaling 20, 11261167.
MohanKumar, K, Namachivayam, K, Ho, TT, Torres, BA, Ohls, RK and Maheshwari, A 2017. Cytokines and growth factors in the developing intestine and during necrotizing enterocolitis. Seminars in Perinatology 41, 5260.
Nabuurs, MJ, Hoogendoorn, A, van der Molen, EJ and van Osta, AL 1993. Villus height and crypt depth in weaned and unweaned pigs, reared under various circumstances in The Netherlands. Research in Veterinary Science 55, 7884.
National Research Council, 2012. Nutrient requirements of swine, 11th revised edition. National Academic Press, Washington, DC, USA.
Pié, S, Lallès, JP, Blazy, F, Laffitte, J, Sève, B and Oswald, IP 2004. Weaning is associated with an upregulation of expression of inflammatory cytokines in the intestine of piglets. The Journal of Nutrition 134, 641647.
Qin, J, Dua, R, Yang, Y, Zhang, H, Li, Q, Liu, L, Guan, H, Hou, J and An, X 2013. Dexamethasone-induced skeletal muscle atrophy was associated with upregulation of myostatin promoter activity. Research in Veterinary Science 94, 8489.
Quaye, IK 2008. Haptoglobin, inflammation and disease. Transactions of the Royal Society of Tropical Medicine and Hygiene 102, 735742.
Ritchie, JC, Belkin, BM, Ranga, K, Krishnan, R, Nemeroff, CB and Caroll, BJ 1990. Plasma dexamethasone concentrations and the dexamethasone suppression test. Biological Psychiatry 27, 159173.
Rosen, A, Brodin, K and Eneroth, P 1992. Short-term restraint stress and s.c. saline injection alter the tissue levels of substance P and cholecystokinin in the peri-aqueductal grey limbic regions of rat brain. Acta veterinaria Scandinavica 146, 342348.
Soler, L, Miller, I, Hummel, K, Razzazi-Fazeli, E, Jessen, F, Escribano, D and Niewold, T 2016. Growth promotion in pigs by oxytetracycline coincides with down regulation of serum inflammatory parameters and of hibernation-associated protein HP-27. Electrophoresis 37, 12771286.
Son, YH, Lee, SJ, Lee, KB, Lee, JH, Jeong, EM, Chung, SG, Park, SC and Kim, IG 2015. Dexamethasone downregulates caveolin-1 causing muscle atrophy via inhibited insulin signaling. Journal of Endocrinology 225, 2737.
Schwarze, J and Bartmann, P 1994. Influence of dexamethasone on lymphocyte proliferation in whole blood cultures of neonates. Biology of the Neonate 65, 295301.
Ulluwishewa, D, Anderson, RC, McNabb, WC, Moughan, PJ, Wells, JM and Roy, NC 2011. Regulation of tight junction permeability by intestinal bacteria and dietary components. Journal of Nutrition 141, 769776.
Vandevyver, S, Dejager, L, Tuckermann, J and Libert, C 2013. New insights into the anti-inflammatory mechanisms of glucocorticoids: An emerging role for glucocorticoid-receptor-mediated transactivation. Endocrinology 154, 9931007.
Wyns, H, Meyer, E, Watteyn, A, Plessers, E, De Baere, S, De Backer, P and Croubels, S 2013. Pharmacokinetics of dexamethasone after intravenous and intramuscular administration in pigs. Veterinary Journal 198, 286288.
Yamamoto, S, Tanabe, M, Wakabayashi, G, Shimazu, M, Matsumoto, K and Kitajima, M 2001. The role of tumor necrosis factor-alpha and interleukin-1beta in ischemia-reperfusion injury of the rat small intestine. The Journal of Surgical Research 99, 134141.



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