Biological Trace Element Research

, Volume 154, Issue 2, pp 275–280 | Cite as

Effects of Norepinephrine on Immune Functions of Cultured Splenic Lymphocytes Exposed to Aluminum Trichloride

  • Ji-Hong Zhang
  • Chong-Wei Hu
  • Yan-Zhu Zhu
  • Shi-Min Liu
  • Chong-Sheng Bai
  • Yan-Fei Han
  • Shi-Liang Xia
  • Yan-Fei LiEmail author


The aim of this study was to investigate the effect of norepinephrine (NE) on spleen lymphocytes exposed to aluminum trichloride (AlCl3). In this experiment, lymphocytes were isolated from spleens of healthy Wistar rats weighing about 130 g and cultured with RPMI-1640 medium containing the final concentration of 0.552 mmol/L AlCl3. NE was added to the cultured cells at the final concentrations of 0 (control group), 0.1 (low-dose group), 1 (mid-dose group), and 10 (high-dose group) nmol/L. No addition of both AlCl3 and NE serviced as blank (BG). The T lymphocyte proliferation; the contents of IL-2, TNF-α, and T lymphocyte subsets; immunoglobulin G (IgG) and intracellular cyclic adenosine monophosphate (cAMP) concentrations; and β2-adrenergic receptor (β2-AR) density were measured at the end of the culture. The result showed that NE decreased T lymphocyte proliferation and the contents of IL-2, TNF-α, and T lymphocyte subsets whereas increased the concentrations of IgG and intracellular cAMP and β2-AR density of the lymphocyte exposed to AlCl3. AlCl3 exposure without adding NE showed the similar impacts on these measures compared with BG. The results suggested that NE aggravated AlCl3 immunotoxicity on the lymphocytes and disordered the immune functions of the lymphocyte through the β2-AR-cAMP signal pathway.


Aluminum trichloride Norepinephrine Splenic lymphocytes Immune functions 



The study was supported by a Grant from the National Science Foundation Project (31172375).

Conflict of Interest

The authors declare that there is no conflict of interest.


  1. 1.
    Willhite CC, Ball GL, McLellan CJ (2012) Total allowable concentrations of monomeric inorganic aluminum and hydrated aluminum silicates in drinking water. Crit Rev Toxicol 42:358–442PubMedCrossRefGoogle Scholar
  2. 2.
    Bondy SC (2010) The neurotoxicity of environmental aluminum is still an issue. Neurotoxicology 31:575–581PubMedCrossRefGoogle Scholar
  3. 3.
    Besedovsky H, Sorkin E (1977) Network of immune–neuroendocrine interactions. Clin Exp Immunol 27:1–12PubMedGoogle Scholar
  4. 4.
    Makino S, Hashimoto K, Gold PW (2002) Multiple feedback mechanisms activating corticotropin-releasing hormone system in the brain during stress. Pharmacol Biochem Behav 73:147–158PubMedCrossRefGoogle Scholar
  5. 5.
    Khan MM, Sansoni P, Silverman ED, Engleman EG, Melmon KL (1986) Beta-adrenergic receptors on human suppressor, helper, and cytolytic lymphocytes. Biochem Pharmacol 35:1137–1142PubMedCrossRefGoogle Scholar
  6. 6.
    Brudvik KW, Taskén K (2012) Modulation of T cell immune functions by the prostaglandin E (2)-cAMP pathway in chronic inflammatory states. Br J Pharmacol 166:411–419PubMedCrossRefGoogle Scholar
  7. 7.
    Kuroki K, Takahashi HK, Iwagaki H, Murakami T, Kuinose M, Hamanaka S, Minami K, Nishibori M, Tanaka N, Tanemoto K (2004) Beta-2-adrenergic receptor stimulation-induced immunosuppressive effects possibly through down-regulation of co-stimulatory molecules, ICAM-l, CD40 and CD14 on monocytes. J Int Med Res 32:465–483PubMedCrossRefGoogle Scholar
  8. 8.
    Vendetti S, Patrizio M, Riccomi A, De Magistris MT (2006) Human CD4+ T lymphocytes with increased intracellular cAMP levels exert regulatory functions by releasing extracellular cAMP. J Leukoc Biol 80:880–888PubMedCrossRefGoogle Scholar
  9. 9.
    Qiu YH, Cheng C, Dai L, Peng YP (2005) Effect of endogenous catecholamines in lymphocytes on lymphocyte function. J Neuroimmunol 167:45–52PubMedCrossRefGoogle Scholar
  10. 10.
    Sylvester PW (2011) Optimization of the tetrazolium dye (MTT) colorimetric assay for cellular growth and viability. Methods Mol Biol 716:157–168PubMedCrossRefGoogle Scholar
  11. 11.
    Caraher EM, Parenteau M, Gruber H, Scott FW (2000) Flow cytometric analysis of intracellular IFN-γ, IL-4 and IL-10 in CD3 + 4+ T cells from rat spleen. J Immunol Methods 244:29–40PubMedCrossRefGoogle Scholar
  12. 12.
    Zhu YZ, Liu DW, Liu ZY, Li YF (2013) Impact of aluminum exposure on the immune system: a mini review. Environ Toxicol Pharmacol 35:82–87PubMedCrossRefGoogle Scholar
  13. 13.
    Bordon Y (2011) Lymphocyte migration: travel agents for two. Nat Rev Immunol 11:77PubMedCrossRefGoogle Scholar
  14. 14.
    Ferrari M, Formasiero MC, Isetta AM (1990) MTT colorimetric assay for testing macrophage cytotoxic activity in vitro. J Immunol Methods 131:165–172PubMedCrossRefGoogle Scholar
  15. 15.
    Qiu YH, Peng YP, Wang JH (1996) Immunoregulatory role of neurotransmitters. Adv Neuroimmunol 6:223–231PubMedCrossRefGoogle Scholar
  16. 16.
    Bartik MM, Brooks WH, Roszman TL (1993) Modulation of T cell proliferation by stimulation of the beta-adrenergic receptor: lack of correlation between inhibition of T cell proliferation and cAMP accumulation. Cell Immunol 148:408–421PubMedCrossRefGoogle Scholar
  17. 17.
    She Y, Wang N, Chen CX, Zhu YZ, Xia SL, Hu CW, Li YF (2012) Effects of aluminum on immune functions of cultured splenic T and B lymphocytes in rats. Bio Trace Elem Res 147:246–250CrossRefGoogle Scholar
  18. 18.
    Stefanski V (2001) Social stress in laboratory rats: behavior, immune function, and tumor metastasis. Physiol Behav 73:385–391PubMedCrossRefGoogle Scholar
  19. 19.
    Saha B, Mondal AC, Majumder J, Basu S, Dasqupta PS (2001) Physiological concentrations of dopamine inhibit the proliferation and cytotoxicity of human CD4+ and CD8+ T cells in vitro: a receptor-mediated mechanism. Neuroimmunomodulation 9:23–33PubMedCrossRefGoogle Scholar
  20. 20.
    Wei XM, Lu JP, Fang QH, Mo LF (2001) Immunotoxicology of AlCl3 on the human T-lymphocyte cultivated in vitro. Chin J Prev Med 35:213–214Google Scholar
  21. 21.
    Zhu YZ, Li XW, Chen CX, Wang F, Li J, Hu CW, Li YF, Li M (2012) Effects of aluminum trichloride on the trace elements and cytokines in the spleen of rats. Food Chem Toxicol 50:2911–2915PubMedCrossRefGoogle Scholar
  22. 22.
    Takayanagi Y, Osawa S, Ikuma M, Takagaki K, Zhang J, Hamaya Y, Yamada T, Sugimoto M, Furuta T, Miyajima H, Sugimoto K (2012) Norepinephrine suppresses IFN-γ and TNF-α production by murine intestinal intraepithelial lymphocytes via the beta-1-adrenoceptor. J Neuroimmunol 245:66–74PubMedCrossRefGoogle Scholar
  23. 23.
    Liang HP, Wang ZG, Zhu PF, Luo Y, Geng B, Xu X (1999) The suppression of T cell functions and its relationship with the change of signal transduction after trauma. Natl Med J China 79:525–528Google Scholar
  24. 24.
    Kalinichenko VV, Mokyr MB, Graf LH Jr, Cohen RL, Chambers DA (1999) Norepinephrine-mediated inhibition of antitumor cytotoxic T lymphocyte generation involves a beta-adrenergic receptor mechanism and decreased TNF-α gene expression. J Immunol 163:2492–2499PubMedGoogle Scholar
  25. 25.
    Kohm AP, Sanders VM (2001) Norepinephrine and beta-2-adrenergic receptor stimulation regulate CD4+ T and B lymphocyte function in vitro and in vivo. Pharmacol Rev 53:487–525PubMedGoogle Scholar
  26. 26.
    Podojil JR, Sanders VM (2003) Selective regulation of mature IgG1 transcription by CD86 and beta-2-adrenergic receptor stimulation. J Immunol 170:5143–5151PubMedGoogle Scholar
  27. 27.
    Kasprowicz DJ, Kohm AP, Berton MT, Chruscinski AJ, Sharpe A, Sanders VM (2000) Stimulation of the B cell receptor, CD86 (B7-2), and the beta-2-adrenergic receptor intrinsically modulates the level of IgG1 and IgE produced per B cell. J Immunol 165:680–690PubMedGoogle Scholar
  28. 28.
    Bailly S, Ferrua B, Fay M, Gougerot-Pocidalo MA (1990) Differential regulation of IL-6, IL-1A, IL-1β and TNF-α production in LPS-stimulated human monocytes: role of cyclic AMP. Cytokine 2:205–210PubMedCrossRefGoogle Scholar
  29. 29.
    Sanders VM, Baker RA, Ramer-Quinn DS, Kasprowicz DJ, Fuchs BA, Street NE (1997) Differential expression of the beta-2-adrenergic receptor by Th1 and Th2 clones: implications for cytokine production and B cell help. J Immunol 158:4200–4210PubMedGoogle Scholar
  30. 30.
    Heijink IH, van den Berge M, Vellenga E, De Monchy JG, Postma DS, Kauffman HF (2004) Altered beta-2-adrenergic regulation of T cell activity after allergen challenge in asthma. Clin Exp Allergy 34:1356–1363PubMedCrossRefGoogle Scholar
  31. 31.
    Severn A, Rapson NT, Hunter CA, Liew FY (1992) Regulation of tumor necrosis factor production by adrenaline and beta-adrenergic agonists. J Immunol 148:3441–3445PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Ji-Hong Zhang
    • 1
  • Chong-Wei Hu
    • 2
  • Yan-Zhu Zhu
    • 3
  • Shi-Min Liu
    • 4
  • Chong-Sheng Bai
    • 1
  • Yan-Fei Han
    • 1
  • Shi-Liang Xia
    • 1
  • Yan-Fei Li
    • 1
    Email author
  1. 1.College of Veterinary MedicineNortheast Agricultural UniversityHarbinPeople’s Republic of China
  2. 2.College of Animals ScienceFujian Agricultural and Forestry UniversityFuzhouPeople’s Republic of China
  3. 3.Institute of Special Economic Animal and Plant ScienceChinese Academy of Agricultural SciencesChangchunPeople’s Republic of China
  4. 4.School of Animal BiologyThe University of Western AustraliaPerthAustralia

Personalised recommendations