Biological Trace Element Research

, Volume 185, Issue 1, pp 162–169 | Cite as

The Antagonistic Effect of Selenium on Lead-Induced Immune Dysfunction via Recovery of Cytokine and Heat Shock Protein Expression in Chicken Neutrophils

  • Mengyuan Xing
  • Xi Jin
  • Jinliang Wang
  • Qunxiang Shi
  • Jingzeng Cai
  • Shiwen XuEmail author


Lead (Pb) is a ubiquitous and toxic heavy metal and it can damage the immune system in humans and animals. Many researchers have reported that Selenium (Se) could possess various pharmacological effects in mammals. However, few studies have been carried out to investigate the protective role of Se in birds, especially in chickens. In this study, we investigated the protective effects of Se against Pb-induced inflammatory responses and the expression of heat shock proteins (HSPs) in peripheral blood neutrophils. One hundred eighty Hy-Line brown chickens were randomly divided into the control group (Con group), Se supplementation group (+Se group), Pb supplementation group (+Pb group), and the Se and Pb compound group (Se+Pb group). On the 90th day of the experiment, the peripheral blood was collected to extract neutrophils, and then, the levels of HSPs and cytokines were examined. The results showed that, after Pb treatment, the levels of IL-(1β, 1R, 4, 8, 10, and 12β), TGF-β4, and HSP (27, 40, 60, 70, and 90) mRNA were significantly increased and levels of IL-2 and IFN-γ mRNA were decreased compared with those in the control group. Compared with the control group, the protein levels of HSP60 and HSP70 were also increased in the Pb treatment group. Co-administration of Se (1 mg/kg/day) and Pb resulted in a reversal of the Pb-induced cytokine changes in neutrophils accompanied by a significant decrease in HSPs. Our study demonstrated that Pb could decrease the immune function via changing the expression of cytokines and HSPs in chicken neutrophils, but Se could relieve the toxic effect induced by Pb.


Lead Selenium Neutrophil Chickens Cytokines Heat shock proteins 


Funding Information

This study was supported by the National Natural Science Foundation of China (31272626) and the International (Regional) Cooperation and Exchange Projects of the National Natural Science Foundation of China (31320103920).

Compliance with Ethical Standards

All procedures used in this study were approved by the Institutional Animal Care and Use Committee of Northeast Agricultural University.

Conflict of Interest

The authors declare that they have no conflicts of interest.


  1. 1.
    Bakalli RI, Pesti GM, Ragland WL (1995) The magnitude of lead toxicity in broiler chickens. Vet Hum Toxicol 37(1):15–19PubMedGoogle Scholar
  2. 2.
    Beulke SH (1999) Casarett and Doull’s toxicology the basic science of poisons, fifth edition companion handbook. Aust J Hosp Pharm 29(1):74–74. CrossRefGoogle Scholar
  3. 3.
    Ciobanu C, Slencu BG, Cuciureanu R (2012) Estimation of dietary intake of cadmium and lead through food consumption. Rev Med Chir Soc Med Nat Iasi 116(2):617–623PubMedGoogle Scholar
  4. 4.
    Hudson C, Cao L, KastenJolly J, Kirkwood J, Lawrence D (2003) Susceptibility of lupus-prone Nzm mouse strains to lead exacerbation of systemic lupus erythematosus symptoms. J Toxicol Environ Health A 66(10):895–918. CrossRefPubMedGoogle Scholar
  5. 5.
    Queiroz ML, Almeida M, Gallão MI, Höehr NF (1993) Defective neutrophil function in workers occupationally exposed to lead. Basic Clin Pharmacol Toxicol 72(2):73–77. CrossRefGoogle Scholar
  6. 6.
    Governa M, Valentino M, Visonà I (1987) In vitro impairment of human granulocyte functions by lead. Arch Toxicol 59(6):421–425. CrossRefPubMedGoogle Scholar
  7. 7.
    Shen X, Lee K, König R (2001) Effects of heavy metal ions on resting and antigen-activated CD4 + T cells. Toxicology 169(1):67–80. CrossRefPubMedGoogle Scholar
  8. 8.
    Binder R, Kress A, Kan G, Herrmann K, Kirschfink M (1999) Neutrophil priming by cytokines and vitamin D binding protein (Gc-globulin): impact on C5a-mediated chemotaxis, degranulation and respiratory burst. Mol Immunol 36(13–14):885–892. CrossRefPubMedGoogle Scholar
  9. 9.
    Chen H, Xu XL, Li YP, Wu JX (2014) Characterization of heat shock protein 90, 70 and their transcriptional expression patterns on high temperature in adult of Grapholita molesta (Busck). Insect Sci 21(4):439–448. CrossRefPubMedGoogle Scholar
  10. 10.
    Lee J, Lim KT (2012) Inhibitory effect of SJSZ glycoprotein (38 kDa) on expression of heat shock protein 27 and 70 in chromium (VI)-treated hepatocytes. Mol Cell Biochem 359(1–2):45–57. CrossRefPubMedGoogle Scholar
  11. 11.
    Yao HD, Wu Q, Zhang ZW, Zhang JL, Li S, Huang JQ, Ren FZ, SW X, Wang XL, Lei XG (2013) Gene expression of endoplasmic reticulum resident selenoproteins correlates with apoptosis in various muscles of se-deficient chicks. J Nutr 143(5):613–619. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Yao HD, Wu Q, Zhang ZW, Li S, Wang XL, Lei XG, Xu SW (2013) Selenoprotein W serves as an antioxidant in chicken myoblasts. Biochim Biophys Acta 1830(4):3112–3120. CrossRefPubMedGoogle Scholar
  13. 13.
    Orun I, Talas ZS, Ozdemir I, Alkan A, Erdogan K (2008) Antioxidative role of selenium on some tissues of (Cd2+, Cr3+)-induced rainbow trout. Ecotoxicol Environ Saf 71(1):71–75. CrossRefPubMedGoogle Scholar
  14. 14.
    Hiroshi S, Noriko Y, Satoshi S (1985) Development of reflexes in neonatal mice prenatally exposed to methylmercury and selenite. Toxicol Lett 25(2):199–203. CrossRefGoogle Scholar
  15. 15.
    Flora SJ, Singh S, Tandon SK (1983) Role of selenium in protection against lead intoxication. Basic Clin Pharmacol Toxicol 53(1):28–32Google Scholar
  16. 16.
    Lai J, Yin S, Xu Q, Hu S (2004) Protection of zinc and selenium content of brain and blood on learning and memory exposed to lead in growing rats. J Hyg Res 33(2):218Google Scholar
  17. 17.
    Cabañero AI, Carvalho C, Madrid Y, Batoréu C, Cámara C (2005) Quantification and speciation of mercury and selenium in fish samples of high consumption in Spain and Portugal. Biol Trace Elem Res 103(1):17–35. CrossRefPubMedGoogle Scholar
  18. 18.
    Li JL, Jiang CY, Li S, Xu SW (2013) Cadmium induced hepatotoxicity in chickens (Gallus domesticus) and ameliorative effect by selenium. Ecotoxicol Environ Saf 96(8):103–109. CrossRefPubMedGoogle Scholar
  19. 19.
    Santos AP, Lucas RL, Andrade V, Mateus ML, Milatovic D, Aschner M, Batoreu MC (2012) Protective effects of ebselen (Ebs) and para-aminosalicylic acid (PAS) against manganese (Mn)-induced neurotoxicity. Toxicol Appl Pharmacol 258(3):394–402. CrossRefPubMedGoogle Scholar
  20. 20.
    Kimmel CA (1979) Effect of chronic developmental lead exposure on cell-mediated immune functions. Clin Exp Immunol 35(3):413–420PubMedPubMedCentralGoogle Scholar
  21. 21.
    Ündeğer Ü, Başaran N (1998) Effects of lead on neutrophil functions in occupationally exposed workers. Environ Toxicol Pharmacol 5(2):113–117. CrossRefPubMedGoogle Scholar
  22. 22.
    Romagnani S (2000) T-cell subsets (Th1 versus Th2). Ann Allergy Asthma Immunol 85(1):9–18. CrossRefPubMedGoogle Scholar
  23. 23.
    Verstrepen L, Bekaert T, Chau TL, Tavernier J, Chariot A, Beyaert R (2008) TLR-4, IL-1R and TNF-R signaling to NF-kB: variations on a common theme. Cell Mol Life Sci 65(19):2964–2978. CrossRefPubMedGoogle Scholar
  24. 24.
    Giraldo S, Sanchez J, Felty Q, Roy D (2009) IL1B (interleukin 1, beta). Atlas Genet Cytogenet Oncol Haematol 13(4):273–275Google Scholar
  25. 25.
    Xu F, Shuang L, Shu L (2015) Effects of selenium and cadmium on changes in the gene expression of immune cytokines in chicken splenic lymphocytes. Biol Trace Elem Res 165(2):1–8CrossRefGoogle Scholar
  26. 26.
    Malek TR, Yu A, Zhu L, Matsutani T, Adeegbe D, Bayer AL (2008) IL-2 family of cytokines in T regulatory cell development and homeostasis. J Clin Immunol 28(6):635–639. CrossRefPubMedGoogle Scholar
  27. 27.
    Liu X, Li Z, Han C, Zhang Z, Xu S (2012) Effects of dietary manganese on Cu, Fe, Zn, Ca, Se, IL-1β, and IL-2 changes of immune organs in cocks. Biol Trace Elem Res 148(3):336–344. CrossRefPubMedGoogle Scholar
  28. 28.
    Overbergh L, Valckx D, Waer M, Mathieu C (1999) Quantification of murine cytokine mRNAs using real time quantitative reverse transcriptase PCR. Cytokine 11(4):305–312. CrossRefPubMedGoogle Scholar
  29. 29.
    Bickel M (1993) The role of interleukin-8 in inflammation and mechanisms of regulation. J Periodontol 64(5 Suppl):456–460PubMedGoogle Scholar
  30. 30.
    Yang Y, Zhang X, Fu Y, Yang H (2014) Leptin and IL-8: two novel cytokines screened out in childhood lead exposure. Toxicol Lett 227(3):172–178. CrossRefPubMedGoogle Scholar
  31. 31.
    Lin YC, Wei PL, Tsai YT, Wong JH, Chang CM, Wang JY, Hou MF, Lee YC, Chuang HY, Chang WC (2015) Pb2+ induced IL-8 gene expression by extracellular signal-regulated kinases and the transcription factor, activator protein 1, in human gastric carcinoma cells. Environ Toxicol 30(3):315–322CrossRefPubMedGoogle Scholar
  32. 32.
    Cuneo AA, Autieri MV (2009) Expression and function of anti-inflammatory interleukins: the other side of the vascular response to injury. Curr Vasc Pharmacol 7(3):267–276. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Villanueva MBG, Koizumi S, Jonai H (2000) Cytokine production by human peripheral blood mononuclear cells after exposure to heavy metals. J Health Sci 46(5):6–21Google Scholar
  34. 34.
    Lebastchi AH, Khan SF, Qin L, Li W, Zhou J, Hibino N, Yi T, Rao DA, Pober JS, Tellides G (2011) TGF-β expression by human vascular cells inhibits IFN-γ production and arterial media injury by alloreactive memory T cells. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg 11(11):2332–2341. CrossRefGoogle Scholar
  35. 35.
    Cao AT, Yao S, Gong B, Elson CO, Cong Y (2012) Th17 cells upregulate polymeric Ig receptor and intestinal IgA and contribute to intestinal homeostasis. J Immunol 189(9):4666–4673. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Jakowlew SB, Mathias A, Lillehoj HS (1997) Transforming growth factor-β isoforms in the developing chicken intestine and spleen: increase in transforming growth factor-β4 with coccidia infection. Vet Immunol Immunopathol 55(4):321–339. CrossRefPubMedGoogle Scholar
  37. 37.
    Sen GC (2001) Viruses and interferons. Annu Rev Microbiol 55(1):255–281. CrossRefPubMedGoogle Scholar
  38. 38.
    Kamińska T, Filar J, Madej E, Szusterciesielska A, Kandeferszerszeń M (1998) Modification of bovine interferon and tumor necrosis factor production by lead in vivo and in vitro. Arch Immunol Ther Exp 46(5):323Google Scholar
  39. 39.
    Sherman M, Multhoff G (2007) Heat shock proteins in cancer. Ann N Y Acad Sci 1113(1):192–201. CrossRefPubMedGoogle Scholar
  40. 40.
    Guo Y, Zhao P, Guo G, Hu Z, Li T, Zhang K, Sun Y, Zhang X, Zhang W, Xing M (2016) Effects of arsenic trioxide exposure on heat shock protein response in the immune organs of chickens. Biol Trace Elem Res 169(1):134–141. CrossRefPubMedGoogle Scholar
  41. 41.
    Sun GX, Chen Y, Liu CP, Li S, Fu J (2016) Effect of selenium against lead-induced damage on the gene expression of heat shock proteins and inflammatory cytokines in peripheral blood lymphocytes of chickens. Biol Trace Elem Res 172(2):474–480. CrossRefPubMedGoogle Scholar
  42. 42.
    Chander K, Vaibhav K, Ahmed ME, Javed H, Tabassum R, Khan A, Kumar M, Katyal A, Islam F, Siddiqui MS (2014) Quercetin mitigates lead acetate-induced behavioral and histological alterations via suppression of oxidative stress, Hsp-70, Bak and upregulation of Bcl-2. Food Chem Toxicol 68(25–26):297–306. CrossRefPubMedGoogle Scholar
  43. 43.
    Li P, Rossman TG (2001) Genes upregulated in lead-resistant glioma cells reveal possible targets for lead-induced developmental neurotoxicity. Toxicol Sci 64(1):90–99. CrossRefPubMedGoogle Scholar
  44. 44.
    Özbal S, Erbil G, Koçdor H, Tuğyan K, Pekçetin Ç, Özoğul C (2008) The effects of selenium against cerebral ischemia-reperfusion injury in rats. Neurosci Lett 438(3):265–269. CrossRefPubMedGoogle Scholar
  45. 45.
    Montgomery JB, Wichtel JJ, Wichtel MG, Mcniven MA, Mcclure JT, Markham F, Horohov DW (2012) Effects of selenium source on measures of selenium status and immune function in horses. Can J Vet Res 76(4):281PubMedPubMedCentralGoogle Scholar
  46. 46.
    Xi J, Zhe X, Xia Z, Chen M, Xu S (2017) The antagonistic effect of selenium on lead-induced apoptosis via mitochondrial dynamics pathway in the chicken kidney. Chemosphere 180:259–266CrossRefGoogle Scholar
  47. 47.
    Zheng C, Fan W, Xiu C, Jian Z, Li Y (2017) Hypericum perforatum extract attenuates behavioral, biochemical, and neurochemical abnormalities in aluminum chloride-induced Alzheimer’s disease rats. Biomed Pharmacother 91:931CrossRefGoogle Scholar
  48. 48.
    Liu LL, Zhang JL, Zhang ZW, Yao HD, Sun G, SW X (2014) Protective roles of selenium on nitric oxide-mediated apoptosis of immune organs induced by cadmium in chickens. Biol Trace Elem Res 159(1–3):199–209. CrossRefPubMedGoogle Scholar
  49. 49.
    Xu Z, Wang Z, Li JJ, Chen C, Zhang PC, Dong L, Chen JH, Chen Q, Zhang XT, Wang ZL (2013) Protective effects of selenium on oxidative damage and oxidative stress related gene expression in rat liver under chronic poisoning of arsenic. Food Chem Toxicol 58(7):1–7. PubMedCrossRefGoogle Scholar
  50. 50.
    Wang H, Li S, Teng X (2015) The antagonistic effect of selenium on lead-induced inflammatory factors and heat shock proteins mRNA expression in chicken livers. Biol Trace Elem Res 171(2):437–444. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Mengyuan Xing
    • 1
  • Xi Jin
    • 1
  • Jinliang Wang
    • 2
  • Qunxiang Shi
    • 1
  • Jingzeng Cai
    • 1
  • Shiwen Xu
    • 1
    Email author
  1. 1.College of Veterinary MedicineNortheast Agricultural UniversityHarbinPeople’s Republic of China
  2. 2.Shandong Binzhou Animal Science & Veterinary Medicine AcademyBinzhouPeople’s Republic of China

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