期刊论文详细信息
BMC Hematology
Inverse correlation between serum interleukin-6 and iron levels among Japanese adults: a cross-sectional study
Nobuyuki Hamajima4  Kenji Wakai2  Takaaki Kondo1  Yoshikazu Kamiya3  Yasuyuki Goto2  Yoko Mitsuda2  Takashi Tamura2  Hiroko Nakagawa2 
[1] Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya, Japan;Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan;Department of Hematology and Oncology, National Hospital Organization, Higashi Nagoya National Hospital, Nagoya, Japan;Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan
关键词: Helicobacter pylori;    Inflammation;    Serum iron;    Serum interleukin-6;   
Others  :  863143
DOI  :  10.1186/2052-1839-14-6
 received in 2013-07-15, accepted in 2014-02-19,  发布年份 2014
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【 摘 要 】

Background

Interleukin-6 (IL-6) is a multifunctional cytokine that is produced by many different cell types, and plays an important role in the regulation of inflammation, immune responses, the acute-phase response, and hematopoiesis. Previous laboratory and clinical studies have shown that IL-6 causes a significant decrease in serum iron levels. Therefore, we conducted an epidemiological study to examine the association between serum IL-6 and iron levels.

Methods

In total, 280 Japanese individuals aged 20–78 years were enrolled when they visited a clinic located in an urban area for Helicobacter pylori (H. pylori) infection tests and subsequent eradication; 65.3% were infected with H. pylori. Subjects with gastric cancer, idiopathic thrombocytopenia, or IL-6 > 10 pg/mL were excluded from the study. Serum iron and IL-6 levels were measured using the 2-nitroso-5-(N-propyl-3-sulfopropylamino) phenol method and chemiluminescence enzyme immunoassay, respectively.

Results

Geometric mean iron and IL-6 levels were 111.5 μg/dL and 1.77 pg/mL, respectively, for men, and 89.4 μg/dL and 1.55 pg/mL, respectively, for women. The logarithm of serum iron levels was negatively correlated with the logarithm of IL-6 levels in men (r = −0.19, p = 0.047), but not in women (r = −0.035, p = 0.65). Regression analysis, adjusted for sex, age, and H. pylori infection status, showed that the logarithm of serum iron levels was significantly associated with a decreased logarithm of IL-6 levels (β = −0.053, p = 0.041). The odds ratio for low serum iron levels adjusted for sex, age, and H. pylori infection status was 7.88 (95% CI 1.29–48.06) in those with an IL-6 level > 4 pg/mL.

Conclusion

Lower serum iron levels are significantly associated with higher serum IL-6 levels among Japanese adults.

【 授权许可】

   
2014 Nakagawa et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Hirano T, Akira S, Taga T, Kishimoto T: Biological and clinical aspects of interleukin 6. Immunol Today 1990, 11:443-449.
  • [2]Horii Y, Muraguchi A, Iwano M, Matsuda T, Hirayama T, Yamada H, Fujii Y, Dohi K, Ishikawa H, Ohmoto Y, Yoshizaki K, Hirano T, Kishimoto T: Involvement of IL-6 in mesangial proliferative glomerulonephritis. J Immunol 1989, 15:3949-3955.
  • [3]Raj DS: Role of interleukin-6 in the anemia of chronic disease. Semin Arthritis Rheum 2009, 38:382-388.
  • [4]Kishimoto T, Akira S, Taga T: Interleukin-6 and its receptor: a paradigm for cytokines. Science 1992, 258:593-597.
  • [5]Nishimoto N, Kishimoto T, Yoshizaki K: Anti-interleukin 6 receptor antibody treatment in rheumatic disease. Ann Rheum Dis 2000, 59(Suppl 1):i21-i127.
  • [6]Krause A, Neitz S, Mägert HJ, Schulz A, Forssmann WG, Schulz-Knappe P, Adermann K: LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett 2000, 480:147-150.
  • [7]Park CH, Valore EV, Waring AJ, Ganz T: Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 2001, 276:7806-7810.
  • [8]Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, Loréal O: A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem 2001, 276:7811-7819.
  • [9]Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, Kahn A, Vaulont S: Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc Natl Acad Sci USA 2001, 98:8780-8785.
  • [10]Ganz T, Nemeth E: Hepcidin and disorders of iron metabolism. Annu Rev Med 2011, 62:347-360.
  • [11]Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T: IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004, 113:1271-1276.
  • [12]Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T: Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood 2003, 101:2461-2463.
  • [13]Nieken J, Mulder NH, Buter J, Vellenga E, Limburg PC, Piers DA, de Vries EG: Recombinant human interleukin-6 induces a rapid and reversible anemia in cancer patients. Blood 1995, 86:900-905.
  • [14]Kemna E, Pickkers P, Nemeth E, van der Hoeven H, Swinkels D: Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood 2005, 106:1864-1866.
  • [15]Caliskan Y, Yelken B, Ozkok A, Gorgulu N, Yazici H, Telci A, Yildiz A: Lower serum prohepcidin levels associated with lower iron and erythropoietin requirements in hemodialysis patients with chronic hepatitis C. BMC Nephrol 2012, 13:56. doi:10.1186/1471-2369-13-56 BioMed Central Full Text
  • [16]Kuo HC, Yang YL, Chuang JH, Tiao MM, Yu HR, Huang LT, Yang KD, Chang WC, Lee CP, Huang YH: Inflammation-induced hepcidin is associated with the development of anemia and coronary artery lesions in Kawasaki disease. J Clin Immunol 2012, 32:746-752.
  • [17]Maruna P, Vokurka M, Lindner J: Plasma hepcidin correlates positively with interleukin-6 in patients undergoing pulmonary endarterectomy. Physiol Res 2011, 60:493-502.
  • [18]Robson-Ansley P, Walshe I, Ward D: The effect of carbohydrate ingestion on plasma interleukin-6, hepcidin and iron concentrations following prolonged exercise. Cytokine 2011, 53:196-200.
  • [19]Basseri RJ, Nemeth E, Vassilaki ME, Basseri B, Enayati P, Shaye O, Bourikas LA, Ganz T, Papadakis KA: Hepcidin is a key mediator of anemia of inflammation in Crohn’s disease. J Crohns Colitis 2013, 7:e286-e291.
  • [20]Ganz T: Hepcidin and iron regulation, 10 years later. Blood 2011, 117:4425-4433.
  • [21]Ganz T: Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 2003, 102:783-788.
  • [22]Falkensammer CE, Thurnher M, Leonhartsberger N, Ramoner R: C-reactive protein is a strong predictor for anaemia in renal cell carcinoma: role of IL-6 in overall survival. BJU Int 2011, 107:1893-1898.
  • [23]Eleftheriadis T, Pissas G, Remoundou M, Filippidis G, Antoniadi G, Oustampasidou N, Liakopoulos V, Stefanidis I: Ferroportin in monocytes of hemodialysis patients and its associations with hepcidin, inflammation, markers of iron status and resistance to erythropoietin. Int Urol Nephrol 2013. [Epub ahead of print]
  • [24]Eguchi A, Mochizuki T, Tsukada M, Kataoka K, Hamaguchi Y, Oguni S, Nitta K, Tsuchiya K: Serum hepcidin levels and reticulocyte hemoglobin concentrations as indicators of the iron status of peritoneal dialysis patients. Int J Nephrol 2012, 2012:239476. doi:10.1155/2012/239476. Epub 2012 Nov 1
  • [25]Schwarz P, Kübler JA, Strnad P, Müller K, Barth TF, Gerloff A, Feick P, Peyssonnaux C, Vaulont S, Adler G, Kulaksiz H: Hepcidin is localised in gastric parietal cells, regulates acid secretion and is induced by Helicobacter pylori infection. Gut 2012, 61:193-201.
  • [26]Lee SY, Song EY, Yun YM, Yoon SY, Cho YH, Kim SY, Lee MH: Serum prohepcidin levels in Helicobacter pylori infected patients with iron deficiency anemia. Korean J Intern Med 2010, 25:195-200.
  • [27]Cherian S, Forbes DA, Cook AG, Sanfilippo FM, Kemna EH, Swinkels DW, Burgner DP: An insight into the relationships between hepcidin, anemia, infections and inflammatory cytokines in pediatric refugees: a cross-sectional study. PLoS One 2008, 3:e4030.
  • [28]Nakagawa H, Tamura T, Mitsuda Y, Kurata M, Goto Y, Kamiya Y, Kondo T, Hamajima N: Association between Helicobacter pylori infection detected by the 13C-urea breath test and low serum ferritin levels among Japanese adults. Helicobacter 2013, 18:309-315.
  • [29]Ganz T, Nemeth E: Hepcidin and iron homeostasis. Biochim Biophys Acta 1823, 2012:1434-1443.
  • [30]Wiltink WF, Kruithof J, Mol C, Bos MG, van Eijk HG: Diurnal and nocturnal variations of the serum iron in normal subjects. Clin Chim Acta 1973, 49:99-104.
  • [31]Sinniah R, Doggart JR, Neill DW: Diurnal variations of the serum iron in normal subjects and in patients with haemochromatosis. Br J Haematol 1969, 17:351-358.
  • [32]Troutt JS, Rudling M, Persson L, Ståhle L, Angelin B, Butterfield AM, Schade AE, Cao G, Konrad RJ: Circulating human hepcidin-25 concentrations display a diurnal rhythm, increase with prolonged fasting, and are reduced by growth hormone administration. Clin Chem 2012, 58:1225-1232.
  • [33]Mortensen RF: C-reactive protein, inflammation, and innate immunity. Immunol Res 2001, 24:163-176.
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