Lactoferrin and Interleukin-6 Interaction in Amniotic Infection

  • Katufumi Otsuki
  • Aki Yoda
  • Yoshiro Toma
  • Yukiko Shimizu
  • Hiroshi Saito
  • Takumi Yanaihara
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 443)


Lactoferrin (Lf) has been found in most biological fluids including amniotic fluid and cervical mucoids in pregnant women, and released from neutrophils in response to the inflammation. As Lf possesses antimicrobial properties, it is widely considered to be an important component of the host defence against microbial infections. It is known that premature labor is caused by amniotic infection with the increase of prostaglandin production. High concentration of the inflammatory cytokines: interleukin-1 β (IL-1 β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in the amniotic fluid has been known. However, changes of Lf in amniotic fluid with infection has not been reported. In the present study, Lf concentrations in amniotic fluid were measured under the intra-uterine infections state and the biological significance of Lf was investigated. The effects of Lf on the IL-6 and IL-6mRNA production in cultured amnion cells were also investigated. The concentrations of Lf and IL-6 in amniotic fluid with CAM were 8.76±0.65 μg/ml and 6.92±4.88 ng/ml (n=28) respectively and both were significantly higher (p<0.01) than those without CAM [0.86±0.81 μg/ml and 0.34±0.25 ng/ml (n=31)]. Significant positive correlation (r=0.91, p<0.01) between Lf and IL-6 levels in amniotic fluid was found. IL-6 production induced by lipopolysaccharide (LPS) (100ng/m1) in cultured amnion cells was significantly inhibited (p<0.05) under the physiological concentration of Lf in amnion. Total RNA was extracted from the amniotic cells by guianizine solution. RT-PCR procedure and product analysis were performed from one µg aliquote of total RNA. β-actin was used as an international standard and c-DNA samples were followed by 30 cycles of PCR. RTPCR product of IL-6 mRNA was detected by Southern hybridization. Expression of IL6mRNA was inhibited by the addition of Lf. From the results, the possibility that Lf might suppress amniotic IL-6 production under the condition of amniotic infection is suggested. It is also suggested that Lf might act as self defence mechanism from intra-uterine infection.


Amniotic Fluid Amniotic Membrane Fetal Membrane Human Lactoferrin Amniotic Fluid Sample 
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  1. 1.
    Arnold RR, Brewer A, Gauthier JJ. (1980) Bactericidal activity of human lactoferrin: sensitivity of a variety of microorganisms. Infect Immun, 28, 893–898PubMedGoogle Scholar
  2. 2.
    Staut J, Norell S, Harrington JP (1984) Kinetic effect of human lactoferrin on the growth of Escherichia coli 011 1. Int J Biochem, 16, 1043–1047.CrossRefGoogle Scholar
  3. 3.
    Ellison RT, Giehl TJ, Laforce MF (1988) Damage of the outer membrane of enteric gram-negative bacteria by lactoferrin and transferrin. Infect Immun, 56, 2774–278I.PubMedGoogle Scholar
  4. 4.
    Suzuki T, Yamauchi K, Kawase K, Kiyosawa I, Okonogi S. (1989) Collaborative bacteriostatic activity of bovine lactoferrin with lysozyme against Escherichia coli 0111. Agric Biol Chem, 53, 1705–1706.CrossRefGoogle Scholar
  5. 5.
    Visca P, Dalmastri C, Verzili D, Antonini G, Chianocone E, Valenti P. (1990) Interaction of lactoferrin with Escherichia coli cells and correlation with antibacterial activity. Med Microbiol Immunol, 179, 323–333.PubMedCrossRefGoogle Scholar
  6. 6.
    Cox T, Mazurier J, Spik G, Montreuil J. Peters TJ (1979) Iron binding proteins and influx of iron across the duodenal brush border. Evidence for specific lactoferrin receptors in the human intestine. Biochim Biophys Acta, 588, 120–128.PubMedCrossRefGoogle Scholar
  7. 7.
    Lonnerdal B (1990) Iron in human milk and cow’s milk–Effects of binding ligands on bioavailability. In: Iron Metabolism in Infants, Lonnerdal B (Ed) CRC Press, Boca Rato, FL, pp 87–107.Google Scholar
  8. 8.
    Broxmeyer H, Gentile P, Cooper S, Lu L, Juliano L, Piacibello W, Meyers LL (1984) Functional activities of acidic isoferritins and lactoferrin in vitro and in vivo. Blood Cells, 10, 397–426.PubMedGoogle Scholar
  9. 9.
    Birgens HS (1991) The interaction of lactoferrin with human monocytes. Dan Med Bull, 38, 244–252.PubMedGoogle Scholar
  10. 10.
    Rudney JD (1989) Relationships between human parotid saliva lysozyme, lactoferrin, salivary peroxidase and secretory immunoglobulin A in a large sample population. Arch Oral Biol, 34, 499–506.PubMedCrossRefGoogle Scholar
  11. 11.
    Cleveland MG, Bakos MA, Hilton SM, Goldblum RH (1991) Amniotic fluid: the first feeding of mucosal immune factors. Adv Exp Med Biol, 310, 41–49.PubMedCrossRefGoogle Scholar
  12. 12.
    Machnicki M, Zimecki M, Zagulski T (1993) Lactoferrin regulates the release of tumour necrosis factor alpha and interleukin 6 in vivo. Int J Exp Pathol, 74, 433–439.PubMedGoogle Scholar
  13. 13.
    Blanc WA (1981) Pathology of the placenta, membranes, and umbilical cord in bacterial, fungal and viral infections in man. In: Perinatal Diseases International Academy of Pathology Monograph, Vol 22, Blanc WA Ed, Williams & Wilkins, Baltimore, pp 67–132.Google Scholar
  14. 14.
    Dipaola C, Mandel ID (1980) Lactoferrin concentration in human parotid saliva as measured by enzyme-linked immunosorbent assay (ELISA) J Dent Res, 59, 1463–1465.PubMedGoogle Scholar
  15. 15.
    Katsufumi O, Aki Y, Kazuhiro H, Yukiko S, Hiroshi S, Takumi Y (1997) Salivary lactoferrin in neonates with chorioamnionitis. The Showa Univ J Med Sci, 9–1, unpublishedGoogle Scholar
  16. 16.
    Chimura T. Hirayama T, Takase M (1993) Lactoferrin in cervical mucus of patients with chorioamnionitis. Jpn Antibiot, 46, 318–322.Google Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Katufumi Otsuki
    • 1
  • Aki Yoda
    • 1
  • Yoshiro Toma
    • 1
  • Yukiko Shimizu
    • 1
  • Hiroshi Saito
    • 1
  • Takumi Yanaihara
    • 1
  1. 1.Department of Obstetrics and GynecologyShowa University School of MedicineTokyoJapan

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