Effects of Zinc Chloride on the Lipopolysaccharide-induced Production of Cytokines in Tumor-bearing Mice

암유발생쥐에 리포폴리사카라이드에 의해 유도된 사이토카인의 생산에 미치는 염화아연의 영향

  • Published : 2001.10.01

Abstract

To determine effects of zinc on lipopolysaccharide (LPS)-induced production of proinflammatory cytokines and Iymphokines in tumor-bearing ICR mice, this study has been investigated. Zinc chloride (Zn) at doses of 1 mg/kg was administered orally 30 minutes before i.p. injection of LPS (8 mg/kg) 5 times for 7 days. LPS greatly increased tumor necrosis factor (TNF)-$\alpha$ and interleukin (IL)-1$\beta$, in both serum and splenic supernatants compared with those in controls. However Zn strongly decreased LPS-increased production of TNF-$\alpha$ and IL-1$\beta$ in spleenic supernatants compared with those in controls and insignificantly also reduced in serum. LPS insignificantly decreased IL-2 levels in spleenic supernatants compared with those in controls but significantly increased interferon (IFN)-${\gamma}$ levels. Zn didn't affect IL-2 production in splenic supernatants compared to controls but significantly enhanced the LPS-decreased production of IL-2. Zn significantly increased IFN-${\gamma}$ levels in splenic supernatants compared to controls and did not affect the LPS-increased production of IFN-${\gamma}$. These findings suggest that Zn may strongly attenuate the LPS-induced pathogenesis of proinflammatory cytokines in tumor-bearing state and significantly up-regulate the LPS-induced function of T cells to produce IL-2 with maintaining normally the LPS- increased levels of IFN-${\gamma}$.

Keywords

References

  1. 약학회지 v.36 no.4 염화아연이 생쥐의 면역반응에 미치는 영향 안영근;김정훈;채병숙;차광재
  2. Am.J.Clin.Nutr. v.68 Zinc and immune function: the biological basis of altered resistance to infection Shankar, A.H.;Prasad, A.S.
  3. Annu.Rev.Nutr. v.10 Zinc deficiency and immune function Keen, C.L.;Gershwin, M.E.
  4. J.Nutr. v.117 Macrophage-mediated depression of T-cell proliferation in zinc-deficiency mice James.S.J.;Swendseid, M.;Makinodan, T.
  5. Nutr.Rep.Int. v.22 Promotion of methylbenzyl-nitrosamine-induced esophageal cancer in rats by subclinical zinc deficiency van Rensburg,S.J.;du Bruyn,D.B.;van Schalkwyk,D.J.
  6. Proc.Assoc.Am.Physicians(CDQ) v.109 no.1 Zinc deficiency: changes in cytokine production and T-cell subpopulations in patients with head and neck cancer and in noncancer subclinical zinc deficiency Prasad, A.S.;Beck, F.W.;Grabowski, S.M.;Kaplan, J.;Mathog, R.H.
  7. Scand.J.Immunol.(UCW) v.31 no.5 Role of zinc in interleukin 2 (IL-2)mediated T-cell activation Tanaka, Y.;Shiozawa, S.;Morimoto, I.;Fujita, T.
  8. J.Biol.Chem.(HIV) v.270 no.38 A regulatory element in the human interleukin 2 gene promoter is a binding site for the zinc finger proteins Sp1 and EGR-1 Skerka, C.;Decker, E.L.;Zipfel, P.E.
  9. Immunopharmacology and immunotoxicology v.14 no.4 Effect of zinc on immune functions and host resistance against infection and tumor challenge Singh, K.P.;Zaidi, S.I.A.;Raisuddin, S.;Saxena, A.K.;Murthy, R.C.;Ray, P.K.
  10. J.Lab.Clin.Med. v.102 Alterations in human natural killer cell activity and moncyte cytotoxicity induced by zinc deficiency Allen, J.I.;Perri, R.T.;McClain, C.J.;Kay, N.E.
  11. Clin.Immunol.Immunpathol v.45 Induction of interferon-γ in human leudocyte cultures stimulated by Zn² Salas,M.;Kirchner, H.
  12. Infect.immunol. v.30 Macrobhages as a sourse of tumoricidal activity (tumor necrotizing factor) Mannel, D.N.;Moore, R.N.;Mergenhagen, S.E.
  13. J.Immunol. v.121 Modulation of immune response by bacterial lipopolysaccharide (LPS);Multigocal efffects of LPS-induced suppression of the primary antibody response to a T-dependent antigen Uchiyama, T.;Jacobs, D.M.
  14. Annu.Rev.Med. v.38 Endotoxins and disease mechanisms Morrison, D.C.;Ryan, J.L.
  15. Clin.Physiol. v.7 Interleukin 1,tumour necrosis factor-α(cachectin)and the pathogenesis of cancer cachexia Moldawer, L.L.;Georgieff, M.;Lundholm.K.
  16. Med.Res.Rev. v.19 The role of cytokines in cancer cachexia Argiles, J.M.;Lopez-Soriano, F.J.
  17. J.Biol.Response Mod. v.9 no.5 Biological resbonse to intravenously administered endotoxin in patients with advanced cancer Engelhardt, R.;Mackensen, A.;Galanos, C.;Andreesen, R.
  18. Acta.Derm.Venereol.(OMQ) v.75 no.1 Protective effect of zinc on keratinocyte activation markers induced by interferon or nickel Gueniche, A.;Viac, J.;Lizard, G.;Charveron, M.;Schmitt, D.
  19. Nutrition(BEU) v.11 Zinc and endothelial function McClain, C.;Morris, P.;Henning, B.
  20. Cancer Research v.53 no.20 Prevention of carcino-genicity of anticancer drugs by metallothionein induction Satoh, M.;Kondo, Y.;Mita, M.;Nakagawa, I.;Naganuma, A.;Imura, N.
  21. Neuropharmacology(NZB) v.35 no.5 Zinc reduces the hyperalgesia and upregulation of NGF and IL-1 beta produced by peripheral inflammation in the rat. Safieh-Garabedian, B.;Poole, S.;Allchorne, A.;Kanaa, S.;Saade, N.;Woolf, C.J.
  22. Immunology(GH7) v.84 no.2 Zinc regulates cytokine induction by superantigens and lipopolysaccharide Driessen, C.;Hirv, K.;Kirchner, H.;Rink, L.
  23. J.Immunol. v.157 no.7 Zinc enhances lipopolysaccharide-induced monokine secretion by alteration of fluidity state of lipopolysaccharide Wellinghausen, N.;Schromm, A.B.;Seydel, U.;Brandenburg, K.;Luhm, J.;Kirchner, H.;Rink, L.
  24. Cancer Epidemiology Biomarkers & Prevention v.8 Vitamin and mineral supplement use is associated with reduced risk of prostate cancer Kristal, A.R.;Stanford, J.L.;Cohen, J.H.;Wicklund, K.;Patterson, R.E.
  25. Neoplasma(NVO) v.46 no.2 Copper, zinc and superoxide dismutase in precancerous, benign diseases and gastric, collrectal and breast cancer Magalova, T.;Bella, V.;Brtkova, A.;Beno, I.;Kudlackova, M.;Volkovova, K.
  26. B.Ssordeted.Karger Baselip Use of mast cell deficient mice to study host parasite relationships in immuno-deficient animals Reed, N.D.;Crowle, P.K.;Ha, T.
  27. Cancr Res. v.51 Role of endogenous tumor necrosis factor α and interleukin 1 for experimental tumor growth and the development of cancer cachexia Gelin, J.;Moldawer, L.L.;Lonnroth, C.;Sherry, B.;Chizzonite,R.;Lundholm, K.
  28. Immunobiology v.188 no.4-5 Tumor-induced macrophage tumor necrosis factor-alpha production suppresses autoreactive T cell proliferation Alleva, D.G.;Burger, C.J.;Elgert, K.D.
  29. J.Immunol v.154 Regulatory mechanisms for production of IFN-gamma and TNF by antitumor T cells or macrophages in the tumor-bearing state Yamamoto, N.;Zou, J.P.;Li, X.F.;Takenaka, H.;Noda, S.;Fujii, T.;Ono, S.;Kobayashi, Y.;Mukaida, N.;Matsushima, K.
  30. J.Exp.Med. v.167 Interleukin 1 potentiates the lethal effect of tumor necrosis factor/cachectin in mice Waage, A.;Espevik, T.
  31. Eur.J.Immunol. v.27 no.10 Zinc inhibits interleukin-1-dependent T cell stimulation Wellinghausen, N.;Martin, M.;RinK, L.
  32. Fed.Proc. v.38 Serum zinc in patients with epidermoid cancer of the head and neck Garofalo, J.A.;Strong, E.;Cunningham-Rundles, S.;Erlandson, E.;Menendez-Botet, C.;Schwartz, M.;Good, R.A.
  33. Infection and Immunity v.68 no.3 Reduced Th1, but not Th2, cytokine production by lymphocytes after in vivo exposure of healthy subjects to endotoxin Lauw, F.N.;ten Hove, T.;Dekkers, P.E.P.;de Jonge.E.;van Deventer, S.J.H.;van der Poll, T.
  34. J.Immunol. v.153 no.7 Endotoxin and lipid A stimulate proliferation of human T cells in the presence of autologous monocytes Mattern, T.;Thanhauser, A.;Reiling, N.;Toelner, K.M.;Duchrow, M.;Kusumoto, S.;Rietschel, E.T.;Ernst, M.;Brade, H.;Flad, H.D.
  35. Med.Hypotheses(MOM) v.49 no.1 Zinc-controlled Th1/Th2 switch significantly determines develoment of diseases Sprietsma, J.E.
  36. Biotechnol.Ther. v.1 The role of cytokines in autoimmunity Chantry, D.;Feldmann, M.