Hostname: page-component-7479d7b7d-fwgfc Total loading time: 0 Render date: 2024-07-12T00:46:58.688Z Has data issue: false hasContentIssue false
  • English
  • Français

Pro-inflammatory cytokine and acute phase protein responses to low-dose lipopolysaccharide (LPS) challenge in pigs

Published online by Cambridge University Press:  09 March 2007

S. Llamas Moya ,
L. Boyle ,
P. B. Lynch  and
S. Arkins
S. Llamas Moya
Affiliation:
Pig Production Department, Teagasc - Moorepark Research Centre, Fermoy, Co. Cork, Ireland Department of Life Sciences, University of Limerick, Limerick, Ireland
L. Boyle
Affiliation:
Pig Production Department, Teagasc - Moorepark Research Centre, Fermoy, Co. Cork, Ireland
P. B. Lynch
Affiliation:
Pig Production Department, Teagasc - Moorepark Research Centre, Fermoy, Co. Cork, Ireland
S. Arkins*
Affiliation:
Department of Life Sciences, University of Limerick, Limerick, Ireland
*
†Corresponding author: E-mail: sean.arkins@ul.ie
Get access

Abstract

The objective of this study was to establish the pro-inflammatory cytokine and acute phase protein responses to low-dose lipopolysaccharide (LPS) challenge in pigs and to determine whether these immune parameters could also be measured in saliva. Possible gender differences in the acute phase reaction were also assessed. At 6 weeks of age, 24 male and 24 female pigs were injected intraperitoneally with a single dose of 0 or 5 μg/kg live weight (LW) of LPS from Escherichia coli (treatment). Matched saliva and blood samples were taken at 0, 2, 4, 8, 12 or 24 h after treatment administration. Samples were analysed for concentrations of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), the acute phase proteins C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin (Hp), and cortisol. Low-dose LPS administration increased plasma levels of TNF-α (P<0·001), CRP (P<0·05) and SAA (P<0·05) but did not affect plasma concentrations of IL-1β or Hp (P>0·1). Treatment by time interactions showed that plasma levels of TNF-α and CRP in LPS-treated pigs peaked at 2 h (P<0·001) and 12 h (P<0·01), respectively. Low-dose LPS injection tended to increase plasma concentrations of cortisol (P=0·056) and the response to LPS differed between genders (P<0·05), with females showing higher cortisol responsiveness to the challenge (P<0·01). Males showed higher levels of both cytokines regardless of the treatment (P<0·05), probably due to the inhibition of cytokine synthesis by cortisol. Concentrations of both pro-inflammatory cytokines were consistently detectable in saliva and were present in higher concentrations than in plasma (P<0·001). Hence, plasma TNF-α, CRP and SAA are useful indicators of sub-acute inflammation/infection in pigs as simulated by a low-dose LPS challenge and gender differences exist in the pro-inflammatory cytokine response after a low dose of LPS.

Keywords

acute phase proteinscytokineslipopolysaccharidespigssex
Type
Research Article
Information
Animal Science , Volume 82 , Issue 4 , August 2006 , pp. 527 - 534
Copyright
Copyright © British Society of Animal Science 2006

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Baumann, H. and Gauldie, J. (1994) The acute phase response. Immunology Today 5: 74–80.CrossRefGoogle Scholar
Beishuizen, A. and Thijs, L. G. (2003) Endotoxin and the hypothalamus-pituitary-adrenal (HPA) axis. Journal of Endotoxin Research 9: 3–24.Google Scholar
Besedovsky, H. O., Del Rey, A., Klusman, I., Furukawa, H., Monge Arditi, G. and Kabiersch, A. (1991) Cytokines as modulators of the hypothalamus-pituitary-adrenal axis. Journal of Steroid Biochemistry and Molecular Biology 40: 613–618.CrossRefGoogle ScholarPubMed
Burrell, R. (1990) Immunomodulation by bacterial endotoxin. Critical Reviews in Microbiology 17: 189–208.CrossRefGoogle ScholarPubMed
Cook, C. J., Mellor, D. J., Harris, P. J., Ingram, J. R. and Matthews, L. R. (2000) Hands-on and hands-off. Measurement of stress. In The biology of animal stress (ed. Moberg, G. P. and Mench, J. A.), pp. 123–146. CAB International, Wallingford.Google Scholar
Da Silva, J. A. P. (1999) Sex hormones and glucocorticoids: interactions with the immune system. Annals of the New York Academy of Sciences 876: 102–117.CrossRefGoogle ScholarPubMed
De Groot, J., Ruis, M. A. W., Scholten, J. W., Koolhaas, J. M. and Boersma, W. J. A. (2001) Long-term effects of social stress on antiviral immunity in pigs. Physiology and Behaviour 73: 145–158.CrossRefGoogle ScholarPubMed
De Jong, I. C., Ekkel, E. D., Burgwal, J. A., Van de Lambooij, E., Korte, S. M., Ruis, M. A. W., Koolhaas, J. M. and Blokhuis, H.J. (1998) Effects of strawbedding on physiological responses to stressors and behaviour in growing pigs. Physiology and Behaviour 64: 303–310.CrossRefGoogle ScholarPubMed
Dugué, B., Ilardo, C., Aimone-Gastin, I., Guéant, J. L., Mouzé-Amady, M., Cnockaert, J. C., Mur, J. M. and Gräsbeck, R. (1996) Cytokines in saliva. Basal concentrations and the effect of high ambient heat (sauna). Stress Medicine 12: 193–197.3.0.CO;2-Z>CrossRefGoogle Scholar
Feghali, C. A. and Wright, T. M. (1997) Cytokines in acute and chronic inflammation. Frontiers in Bioscience 2: 12–26.Google ScholarPubMed
Frank, J. W., Carroll, J. A., Allee, G. L. and Zannelli, M. E. (2003) The effects of thermal environment and spray-dried plasma on the acute-phase response of pigs challenged with lipopolysaccharide. Journal of Animal Science 81: 1166–1176.CrossRefGoogle ScholarPubMed
Frank, J. W., Mellencamp, M. A., Carroll, J. A., Boyd, R. D. and Allee, G. L. (2005) Acute feed intake and acute-phase protein responses following a lipopolysaccharide challenge in pigs from two dam lines. Veterinary Immunology and Immunopathology 107: 179–187.CrossRefGoogle ScholarPubMed
Gaillard, R. C. and Spinedi, E. (1998) Sex- and stress-steroids interactions and the immune system: evidence for a neuroendocrine-immunological sexual dimorphism. Domestic Animal Endocrinology 15: 345–352.CrossRefGoogle ScholarPubMed
Griffin, M. K. and Minton, J. E. (1991) Free-running rhythms of adrenocorticotropic hormone (ACTH), cortisol and melatonin in pigs. Domestic Animal Endocrinology 8: 201–208.CrossRefGoogle Scholar
Grossman, C. J. (1990) Are there underlying immune-neuroendocrine interactions responsible for immunological sexual dimorphism? Progress in Neuroendocrinoimmunology 3: 75–82.Google Scholar
Johnson, R. W. (1997) Inhibition of growth by pro-inflammatory cytokines: an integrated view. Journal of Animal Science 75: 1244–1255.CrossRefGoogle ScholarPubMed
Johnson, R. W. and Von Borell, E. (1994) Lipopolysaccharide-induced sickness behaviour in pigs is inhibited by pretreatment with indomethacin. Journal of Animal Science 72: 309–314.CrossRefGoogle Scholar
Johnson, R. W., Propes, M. J. and Shavit, Y. (1996) Corticosterone modulates behavioral and metabolic effects of lipopolysaccharide. American Journal of Physiology 270: R192–R198.Google ScholarPubMed
Kanitz, E., Tuchscherer, M., Tuchscherer, A., Stabenow, B. and Manteuffel, G. (2002) Neuroendocrine and immune responses to acute endotoxemia in suckling and weaned piglets. Biology of the Neonate 81: 203–209.CrossRefGoogle ScholarPubMed
Krueger, J. M., Obal, F. J., Fang, J., Kubota, T. and Taishi, P. (2001) The role of cytokines in physiological sleep regulation. Annals of the New York Academy of Sciences 933: 211–221.CrossRefGoogle ScholarPubMed
Kushner, I. (1993) Regulation of the acute phase response by cytokines. Perspectives in Biology and Medicine 36: 611–622.CrossRefGoogle ScholarPubMed
Lomniczi, A., Mohn, C., Faletti, A., Franchi, A., McCann, S. M., Rettori, V. and Elverdin, J. C. (2001). Inhibition of salivary secretion by lipopolysaccharide: possible role of prostaglandins. American Journal of Physiology 281: E405–E411.Google ScholarPubMed
Maier, S. F. and Watkins, L. R. (1999) Bidirectional communication between the brain and the immune system: Implications for behaviour. Animal Behaviour 57: 741–751.CrossRefGoogle Scholar
Munck, A. and Náray-Fejes-Tóth, A. (1994) Glucocorticoids and stress: permissive and suppressive actions. Annals of the New York Academy of Sciences 746: 115–130.CrossRefGoogle ScholarPubMed
Olsen, N. J. and Kovacs, W. J. (1996) Gonadal steroids and immunity. Endocrine Reviews 17: 369–384.Google ScholarPubMed
Orellana, R. A., O'Connor, P. M. J., Nguyen, H. V., Bush, J. A., Suryawan, A., Thivierge, M. C., Fiorotto, M. L. and Davis, T. A. (2002). Endotoxemia reduces skeletal muscle protein synthesis in neonates. American Journal of Physiology 283: E909–E916.Google ScholarPubMed
Otten, W., Kanitz, E., Tuchscherer, M. and Nürnberg, G. (2001) Effects of prenatal stress on hypothalamic-pituitary-adrenocortical and sympatho-adrenomedullary axis in neonatal pigs. Animal Science 73: 279–287.Google Scholar
Petersen, H. H., Nielsen, J. P. and Heegaard, P. M. H. (2004) Application of acute phase protein measurements in veterinary clinical chemistry. Veterinary Research 35: 163–187.CrossRefGoogle ScholarPubMed
Rettori, V., Lomniczi, A., Elverdin, J. C., Suburo, A., Faletti, A., Franchi, A. and McCann, S. M. (2000) Control of salivary secretion by nitric oxide and its role in neuroimmunomodulation. Annals of the New York Academy of Sciences 917: 258–267.CrossRefGoogle ScholarPubMed
Richards, C. D. (1998) Interleukin-6. In Cytokines (ed. Mire-Sluis, A. and Thorpe, R.), pp. 87–108. Academic Press, London.CrossRefGoogle Scholar
Sapolsky, R. M., Romero, M. and Munck, A. U. (2000) How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocrine Reviews 21: 55–89.Google ScholarPubMed
Schwarzenberger, F., Toole, G. S., Christie, H. L. and Raeside, J. I. (1993) Plasma levels of several androgens and estrogens from birth to puberty in male domestic pigs. Acta Endocrinologica 128: 173–177.Google ScholarPubMed
Spinedi, E., Suescun, M. O., Hadid, R., Daneva, T. and Gaillard, R. C. (1992) Effects of gonadectomy and sex hormone theraphy on the endotoxin-stimulated hypothalamus-pituitary-adrenal axis: evidence for a neuroendocrine-immunological sexual dimorphism. Endocrinology 131: 2430–2436.CrossRefGoogle Scholar
Statistical Analysis Systems Institute. (1999) Statistical analysis systems version 8. SAS Inc., Cary, NC.Google Scholar
Sugawara, S., Uehara, A., Tamai, R. and Takada, H. (2002) Innate immune responses in oral mucosa. Journal of Endotoxin Research 8: 465–468.CrossRefGoogle ScholarPubMed
Tuchscherer, M., Kanitz, E., Puppe, B., Tuchscherer, A. and Stabenow, B. (2004) Effects of postnatal social isolation on hormonal and immune responses of pigs to an acute endotoxin challenge. Physiology and Behaviour 82: 503–511.CrossRefGoogle Scholar
Turnbull, A. V. and Rivier, C. (1999) Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: actions and mechanisms of action. Physiology Reviews 79: 1–71.CrossRefGoogle ScholarPubMed
Vining, R. F., McGinley, R. A. and Symons, R. G. (1983) Hormones in saliva: mode of entry and consequent implications for clinical interpretation. Clinical Chemistry 29: 1752–1756.CrossRefGoogle ScholarPubMed
Warren, E. J., Finck, B. N., Arkins, S., Kelley, K. W., Scamurra, R. W., Murtaugh, M. P. and Johnson, R. W. (1997) Coincidental changes in behaviour and plasma cortisol in unrestrained pigs after intracerebroventricular injection of tumor necrosis factor-α. Endocrinology 138: 2365–2371.CrossRefGoogle ScholarPubMed
Webel, D. M., Finck, B. N., Baker, D. H. and Johnson, R. W. (1997) Time course of increased plasma cytokines, cortisol, and urea nitrogen in pigs following intraperitoneal injection of lipopolysaccharide. Journal of Animal Science 75: 1514–1520.CrossRefGoogle ScholarPubMed
Wright, K. J., Balaji, R., Hill, C. M., Dritz, S. S., Knoppel, E. L. and Minton, J. E. (2000) Integrated adrenal, somatotropic, and immune responses of growing pigs to treatment with lipopolysaccharide. Journal of Animal Science 78: 1892–1899.CrossRefGoogle ScholarPubMed
Zabel, P., Linnemann, K. and Schlaak, M. (1993) [Circadian rhythms in cytokines.]. Immunitat und Infektion 1: 38–40.Google Scholar