Animal Production Science Animal Production Science Society
Food, fibre and pharmaceuticals from animals
RESEARCH ARTICLE

Adding a bio-response modifier and zinc oxide to piglet weaner diets influences immunological responses to weaning

Ujjwal Kumar De A F , Reena Mukherjee A , Chandan Prakash B , Bhimnere Hanumanthagouda Manjunatha Patel C , Sukdeb Nandi B , Umesh Dimri A , Ashok Kumar Verma D and Med Ram Verma E
+ Author Affiliations
- Author Affiliations

A Division of Medicine, Indian Veterinary Research Institute, Izatnagar 243 122 (Uttar Pradesh), India.

B CADRAD, Indian Veterinary Research Institute, Izatnagar 243 122 (Uttar Pradesh), India.

C Livestock Production and Management Section, Indian Veterinary Research Institute, Izatnagar 243 122 (Uttar Pradesh), India.

D Division of Animal Nutrition, Indian Veterinary Research Institute, Izatnagar 243 122 (Uttar Pradesh), India.

E Division of Livestock Economics, Statistics and Information Technology, Indian Veterinary Research Institute, Izatnagar 243 122 (Uttar Pradesh), India.

F Corresponding author. Email: ujjwalde@gmail.com

Animal Production Science - https://doi.org/10.1071/AN16332
Submitted: 19 May 2016  Accepted: 11 October 2017   Published online: 7 February 2018

Abstract

The effect of zinc oxide (ZnO) and a Mycobacterium smegmatis-derived bio-response modifier (BRM) supplementation on blood neutrophil functions, high-mobility group box 1 (HMGB1) protein and pro-inflammatory cytokine responses was studied in early weanling piglets. In total, 45 piglets were placed in the following five groups: basal diet only (I), supplemented with ZnO (II), supplemented with BRM (III), supplemented with ZnO plus BRM (IV) in basal diet and basal diet without weaning from dam (V). The phagocytic activity, superoxide anion and myeloperoxidase production in blood neutrophils and the concentrations of HMGB1, TNF-α, IFN-γ and IL-1β in blood plasma were measured before and after weaning. The neutrophil functions were impaired and the concentrations of HMGB1, inflammatory cytokines, were elevated in piglets during the post-weaning period. The neutrophil functions were not improved until Day 7 of weaning (P > 0.05) and pronounced elevation (P < 0.05) in the concentration of pro-inflammatory cytokines and HMGB1 was observed until Days 14 and 21 respectively, in Groups II and III. The addition of BRM plus ZnO in basal diet improved superoxide anion and myeloperoxidase production on Day 2 (P < 0.05) and decreased the TNF-α and IFN-γ concentrations on Day 7 (P < 0.05), with no significant change in the level of IL-1β and HMGB1 in Group IV. Finally, it is concluded that addition of ZnO plus BRM in the diet induced the neutrophil functions and reduced the inflammatory cytokine response much earlier to stimulate innate immunity than did ZnO or BRM alone.

Additional keywords: HMGB1, Mycobacterium smegmatis, phagocytic activity, piglet, weaning.


References

Adam A, Lederer E (1984) Muramyl peptides: immunomodulators, sleep factors, and vitamins. Medicinal Research Reviews 4, 111–152.
Muramyl peptides: immunomodulators, sleep factors, and vitamins.CrossRef | 1:CAS:528:DyaL2cXktVSjsL0%3D&md5=e491d1180f4300c454fe540f482ce18cCAS |

Azuma I, Ribi EE, Meyer TJ, Zbar B (1974) Biologically active components from mycobacterial cell walls. I. Isolation and composition of cell wall skeleton and component P3. Journal of the National Cancer Institute 52, 95–101.
Biologically active components from mycobacterial cell walls. I. Isolation and composition of cell wall skeleton and component P3.CrossRef | 1:CAS:528:DyaE2cXhtFGqsrc%3D&md5=2155a7ba07fe982fd24c8967113905cbCAS |

Bera AK, Bhattacharya D, Pan D, Manna B, Bandyopadhyay S, Das SK (2010) Effect of heat killed Mycobacterium phlei on body weight gain and management of caecal coccidiosis in broiler chickens. Research in Veterinary Science 89, 196–199.
Effect of heat killed Mycobacterium phlei on body weight gain and management of caecal coccidiosis in broiler chickens.CrossRef | 1:STN:280:DC%2BC3cjotlCjsA%3D%3D&md5=f45b1155d4c2db8c4c2894e3221a4071CAS |

Blecha F, Pollmann DS, Nichols DA (1983) Weaning pigs at an early age decreases cellular immunity. Journal of Animal Science 56, 396–400.
Weaning pigs at an early age decreases cellular immunity.CrossRef | 1:STN:280:DyaL3s7osFOmsA%3D%3D&md5=9b7459166efc1d47bb7742d3d9a3c3ddCAS |

Bonnette ED, Kornegay ET, Lindemann MD, Hammerberg C (1990) Humoral and cell mediated immune response and performance of weaned pigs fed supplemental vitamin E levels and housed at two nursery temperatures. Journal of Animal Science 68, 1337–1345.
Humoral and cell mediated immune response and performance of weaned pigs fed supplemental vitamin E levels and housed at two nursery temperatures.CrossRef | 1:CAS:528:DyaK3cXkt1anu7g%3D&md5=1b05c532d59f6fa35ac9564a95f4239dCAS |

Boyne R, Arthur JR (1979) Alteration of neutrophil function in selenium-deficient cattle. Journal of Comparative Pathology 89, 151–158.
Alteration of neutrophil function in selenium-deficient cattle.CrossRef | 1:STN:280:DyaE1M7jtVyhug%3D%3D&md5=d1aba796bf3143609f5ec3fff4d2cc5fCAS |

Bretz U, Baggiolini M (1974) Biochemical and morphological characterization of azurophilic and specific granules of human neutrophilic polymorphonuclear leucocytes. The Journal of Cell Biology 63, 251–269.
Biochemical and morphological characterization of azurophilic and specific granules of human neutrophilic polymorphonuclear leucocytes.CrossRef | 1:CAS:528:DyaE2cXltlekt7c%3D&md5=6941ccc1625e4befba88e21aa07d5e5fCAS |

BSAS (2003) ‘Nutrient requirement standards for pigs.’ 2nd edn. (British Society of Animal Science: Penicuik, UK)

Campbell JM, Crenshaw JD, Polo J (2013) The biological stress of early weaned piglets. Journal of Animal Science and Biotechnology 4, 19
The biological stress of early weaned piglets.CrossRef |

Chai W, Zakrzewski SS, Günzel D, Pieper R, Wang Z, Twardziok S, Janczyk P, Osterrieder N, Burwinkel M (2014) High-dose dietary zinc oxide mitigates infection with transmissible gastroenteritis virus in piglets. BMC Veterinary Research 10, 75
High-dose dietary zinc oxide mitigates infection with transmissible gastroenteritis virus in piglets.CrossRef |

Chen G, Li J, Ochani M, Rendon-Mitchell B, Qiang X, Susarla S, Ulloa L, Yang H, Fan S, Goyert SM, Wang P, Tracey KJ, Sama AE, Wang H (2004) Bacterial endotoxin stimulates macrophages to release HMGB1 partly through CD14- and TNF-dependent mechanisms. Journal of Leukocyte Biology 76, 994–1001.
Bacterial endotoxin stimulates macrophages to release HMGB1 partly through CD14- and TNF-dependent mechanisms.CrossRef | 1:CAS:528:DC%2BD2cXpvVCju7c%3D&md5=4b6179ef0afd43fa8897bf9e4581cab5CAS |

Cromwell GL (2002) Why and how antibiotics are used in swine production. Animal Biotechnology 13, 7–27.
Why and how antibiotics are used in swine production.CrossRef |

Davis ME, Brown DC, Maxwell CV, Johnson ZB, Kegley EB, Dvorak RA (2004) Effect of phosphorylated mannans and pharmacological additions of zinc oxide on growth and immunocompetence of weanling pigs. Journal of Animal Science 82, 581–587.
Effect of phosphorylated mannans and pharmacological additions of zinc oxide on growth and immunocompetence of weanling pigs.CrossRef | 1:CAS:528:DC%2BD2cXhtFSmu7w%3D&md5=f6e85bd44e3120f9bb0d029f15a10c64CAS |

De UK, Mukherjee R, Nandi S, Patel BHM, Dimri U, Ravishankar C, Verma AK (2014) Alterations in oxidant/antioxidant balance, high-mobility group box 1 protein and acute phase response in cross-bred suckling piglets suffering from rotaviral enteritis. Tropical Animal Health and Production 46, 1127–1133.
Alterations in oxidant/antioxidant balance, high-mobility group box 1 protein and acute phase response in cross-bred suckling piglets suffering from rotaviral enteritis.CrossRef |

Driessen C, Hirv K, Rink L, Kirchner H (1994) Induction of cytokines by zinc ions in human peripheral blood mononuclear cells and separated monocytes. Lymphokine and Cytokine Research 13, 15–20.

Field TR, Williams MR, Bunch KJ (1985) An improved method for the isolation of a neutrophil-rich fraction from porcine blood. The British Veterinary Journal 141, 355–361.
An improved method for the isolation of a neutrophil-rich fraction from porcine blood.CrossRef | 1:STN:280:DyaL2M3otFarsw%3D%3D&md5=f0905eea9a302fa33b34291084ef1fe6CAS |

Gallois M, Oswald IP (2008) Immunomodulators as efficient alternatives to in -feed antimicrobials in pig production? Archiva Zootechnica 11, 15–32.

Hohenshell LM, Cunnick JE, Ford SP, Kattesh HG, Zimmerman DR, Wilson ME, Matteri RL, Carroll JA, Lay DC (2000) Few differences found between early- and late-weaned pigs raised in the same environment. Journal of Animal Science 78, 38–49.
Few differences found between early- and late-weaned pigs raised in the same environment.CrossRef | 1:CAS:528:DC%2BD3cXhtVagurg%3D&md5=f42bf607a5c02c3e25b23296b9d777daCAS |

Hu CH, Xiao K, Luan ZS, 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, 1094–1101.
Early weaning increases intestinal permeability, alters expression of cytokine and tight junction proteins, and activates mitogen-activated protein kinases in pigs.CrossRef | 1:CAS:528:DC%2BC3sXmsFKnt7c%3D&md5=2b7e44cd6b70513cc80f5c5d141b8ea1CAS |

Ibs KH, Rink L (2003) Zinc-altered immune function. The Journal of Nutrition 133, 1452S–1456S.

Kalinina N, Agrotis A, Antropova Y, DiVitto G, Kanellakis P, Kostolias G, Ilyinskaya O, Tararak E, Bobik A (2004) Increased expression of the DNA-binding cytokine HMGB1 in human atherosclerotic lesions. Role of activated macrophages and cytokines. Arteriosclerosis, Thrombosis, and Vascular Biology 24, 2320–2325.
Increased expression of the DNA-binding cytokine HMGB1 in human atherosclerotic lesions. Role of activated macrophages and cytokines.CrossRef | 1:CAS:528:DC%2BD2cXhtVaisr3E&md5=f1ccd6c9d63b89ae602a084165c6b27eCAS |

Kato S, Hussein MH, Kakita H, Goto T, Daoud GA, Kato T, Sugiura T, Nobata M, Nakajima Y, Endo T, Mizuno K, Ito T, Kato I, Suzuki S, Togari H (2009) Edaravone, a novel free radical scavenger, reduces high-mobility group box 1and prolongs survival in a neonatal sepsis model. Shock 32, 586–592.
Edaravone, a novel free radical scavenger, reduces high-mobility group box 1and prolongs survival in a neonatal sepsis model.CrossRef | 1:CAS:528:DC%2BD1MXhsFOmsbjL&md5=9232f2558604b3bda2a68aa69121f73aCAS |

Keen CL, Gershwin ME (1990) Zinc deficiency and immune function. Annual Review of Nutrition 10, 415–431.
Zinc deficiency and immune function.CrossRef | 1:CAS:528:DyaK3cXlsFWitLw%3D&md5=3b7eee6fd6df6fa296b5690e67984197CAS |

Kim YJ, Kang JH, Yang MP (2009) Zinc increases the phagocytic capacity of canine peripheral blood phagocytes in vitro. Veterinary Research Communications 33, 251–261.
Zinc increases the phagocytic capacity of canine peripheral blood phagocytes in vitro.CrossRef |

Lima AS, Weigel RA, Morgado AA, Nunes GR, Souza FN, Moreno AM, Della Libera AMMP, Sucupira MCA (2012) Parenteral administration of vitamins A, D and E on the oxidative metabolism and function of polymorphonuclear leukocytes in swine. Pesquisa Veterinaria Brasileira 32, 727–734.
Parenteral administration of vitamins A, D and E on the oxidative metabolism and function of polymorphonuclear leukocytes in swine.CrossRef |

Lotze MT, Tracey KJ (2005) High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nature Reviews. Immunology 5, 331–342.
High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal.CrossRef | 1:CAS:528:DC%2BD2MXivVarsr8%3D&md5=3a62a11d2f0a2f3aa846e9dd677f33aaCAS |

Mazzoni M, Merialdi G, Sarli G, Trevisi P, Bosi P (2010) Effect of two doses of different zinc sources (inorganic vs. chelated form) on the epithelial proliferative activity and the apoptotic index of intestinal mucosa of early-weaned pigs orally challenged with E. coli K88. Asian-Australasian Journal of Animal Sciences 23, 777–785.
Effect of two doses of different zinc sources (inorganic vs. chelated form) on the epithelial proliferative activity and the apoptotic index of intestinal mucosa of early-weaned pigs orally challenged with E. coli K88.CrossRef | 1:CAS:528:DC%2BC3cXpt1ait70%3D&md5=6bcf7a42d6b7182b36d7944ec549e207CAS |

McLamb BL, Gibson AJ, Overman EL, Stahl C, Moeser AJ (2013) Early weaning stress in pigs impairs innate mucosal immune responses to enterotoxigenic E. coli challenge and exacerbates intestinal injury and clinical disease. PLoS One 8, e59838
Early weaning stress in pigs impairs innate mucosal immune responses to enterotoxigenic E. coli challenge and exacerbates intestinal injury and clinical disease.CrossRef | 1:CAS:528:DC%2BC3sXntFalt78%3D&md5=590e8dd22d8291aab064d0bc61def279CAS |

Mukherjee R, Ram GC, Dash PK, Goswami T (2004) The activity of milk leucocytes in response to a water soluble fraction of Mycobacterium phlei in bovine subclinical mastitis. Veterinary Research Communications 28, 47–54.
The activity of milk leucocytes in response to a water soluble fraction of Mycobacterium phlei in bovine subclinical mastitis.CrossRef | 1:STN:280:DC%2BD2c%2FpvFaisg%3D%3D&md5=79b3388196c837f07783120395bc2be1CAS |

Nagahata H, Yatsu A, Noda H (1986) The evaluation of a quantitative assay for estimating the bactericidal activity of bovine neutrophils by nitroblue tetrazolium reduction. The British Veterinary Journal 142, 578–584.
The evaluation of a quantitative assay for estimating the bactericidal activity of bovine neutrophils by nitroblue tetrazolium reduction.CrossRef | 1:STN:280:DyaL2s3ktlCnsQ%3D%3D&md5=83661274c87da53dcadd0e6d7acbabdeCAS |

National Research Council (1998) ‘Nutrient requirements of swine.’ 10th rev. edn. (National Academies Press: Washington, DC)

Ravlić-Gulan J, Radosevic-Stasic B, Trobonjaca Z, Petkovic M, Cuk M, Rukavina D (1999) On the role of T lymphocytes in stimulation of humoral immunity induced by peptidoglycan-monomer linked with zinc. International Archives of Allergy and Immunology 119, 13–22.
On the role of T lymphocytes in stimulation of humoral immunity induced by peptidoglycan-monomer linked with zinc.CrossRef |

Ravlić-Gulan J, Radosevic-Stasic B, Gulan G, Stimac D, Pavelic K, Rukavina D (2000) Immunoprotective properties of peptidoglycan monomer linked with zinc in cholestatic jaundice. International Archives of Allergy and Immunology 123, 354–364.
Immunoprotective properties of peptidoglycan monomer linked with zinc in cholestatic jaundice.CrossRef |

Reijnders L (2006) Antimicrobial growth promoters: consumer concerns and demands. In ‘Antimicrobial growth promoters: where do we go to from here?’ (Eds D Barug, J Jong, AK Kries, MWA Verstegen) pp. 59–67. (Wageningen Academic Publishers: Wageningen, The Netherlands)

Rogan D, Fumuso E, Rodriguez E, Wade J, Sanchez Bruni SF (2007) Use of a mycobacterial cell wall extract (MCWE) in susceptible mares to clear experimentally induced endometritis with Streptococcus zooepidemicus. Journal of Equine Veterinary Science 27, 112–117.
Use of a mycobacterial cell wall extract (MCWE) in susceptible mares to clear experimentally induced endometritis with Streptococcus zooepidemicus.CrossRef |

Salas M, Kirchner H (1987) Induction of interferon-γ in human leukocyte cultures stimulated by Zn2+. Clinical Immunology and Immunopathology 45, 139–142.
Induction of interferon-γ in human leukocyte cultures stimulated by Zn2+.CrossRef | 1:CAS:528:DyaL2sXlvFKht7c%3D&md5=3d9d32e71f340bb0a3b65b93837f6ca4CAS |

Schmied J, Rupa P, Garvie S, Wilkie B (2012) Effect of heat-killed Escherichia coli, lipopolysaccharide, and muramyl dipeptide treatments on the immune response phenotype and allergy in neonatal pigs sensitized to the egg white protein ovomucoid. Clinical and Vaccine Immunology; CVI 19, 1955–1964.
Effect of heat-killed Escherichia coli, lipopolysaccharide, and muramyl dipeptide treatments on the immune response phenotype and allergy in neonatal pigs sensitized to the egg white protein ovomucoid.CrossRef | 1:CAS:528:DC%2BC38XhvVWnsr3O&md5=416fa9109a78697f2705c0e77886552eCAS |

Tang D, Shi Y, Kang R, Li T, Xiao W, Wang H, Xiao X (2007) Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1. Journal of Leukocyte Biology 81, 741–747.
Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1.CrossRef | 1:CAS:528:DC%2BD2sXisFCmtrY%3D&md5=e526f2583cc960875359306c9369f140CAS |

Tewari AK, Sharma NN, Rao JR, Mishra AK, Das SK (1996) Effect of Mycobacterium phlei on the development of immunity to Babesia bigemina. Veterinary Parasitology 62, 223–230.
Effect of Mycobacterium phlei on the development of immunity to Babesia bigemina.CrossRef | 1:STN:280:DyaK283jslequg%3D%3D&md5=50018ce1b25f6a6051a56438e8815d4bCAS |

Trckova M, Lorencova A, Hazova K, Sramkova Zajacova Z (2015) Prophylaxis of post-weaning diarrhoea in piglets by zinc oxide and sodium humate. Veterinarni Medicina 60, 351–360.
Prophylaxis of post-weaning diarrhoea in piglets by zinc oxide and sodium humate.CrossRef |

Wang H, Ward MF, Fan XG, Sama AE, Li W (2006) Potential role of high mobility group box 1 in viral infectious diseases. Viral Immunology 19, 3–9.
Potential role of high mobility group box 1 in viral infectious diseases.CrossRef |

Wang Z, Guo Y, Yuan J, Zhang B (2008) Effect of dietary β-1,3/1,6-glucan supplementation on growth performance, immune response and plasma prostaglandin E2, growth hormone and ghrelin in weanling piglets. Asian-Australasian Journal of Animal Sciences 21, 707–714.
Effect of dietary β-1,3/1,6-glucan supplementation on growth performance, immune response and plasma prostaglandin E2, growth hormone and ghrelin in weanling piglets.CrossRef | 1:CAS:528:DC%2BD1cXos1aqsrY%3D&md5=8674daaafae8fe28325cc9c9f32c8d8cCAS |

Zeh HJ, Lotze MT (2005) Addicted to death: invasive cancer and the immune response to unscheduled cell death. Journal of Immunotherapy 28, 1–9.
Addicted to death: invasive cancer and the immune response to unscheduled cell death.CrossRef |



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