title: Bovine lactoferrin enhances proliferation of human peripheral blood lymphocytes and induces cytokine production in whole blood cultures.
abstract: BACKGROUND
  Lactoferrin belongs to the immunoregulatory milk proteins involved in iron metabolism as well in providing innate immunity to newborns. The protein has been the subject of numerous clinical studies.
  
  
  OBJECTIVE
  The aim of this investigation was to evaluate the effects of bovine lactoferrins (bLF), differing in source and iron content, on spontaneous proliferation of human peripheral blood mononuclear cells (PBMC) and cytokine production by human whole blood cultures.
  
  
  METHODS
  The following bLF preparations were used: partially iron saturated or devoid of iron bLF from milk and bLF from colostrum. The study was conducted on 12 healthy volunteers (men, 20-24 years old). The effects of bLFs on the proliferation of PBMC in four-day cultures was studied at 50-0.6 µg/mL concentration range and the rate of proliferation was determined using the MTT colorimetric method. TNF α and IL-6 levels, induced by the bLFs in 24 h whole blood cultures, were measured by ELISA.
  
  
  RESULTS
  The lactoferrins stimulated autologous proliferation of human peripheral blood mononuclear cells (PBMC) in a dose-dependent manner, with a comparable efficacy. This stimulation occurred both in the constant presence of bLFs in the cultures and also upon preincubation of PBMC with bLFs with subsequent exhaustive wash of cells. Only bLF from colostrum induced production of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in cultures of whole blood cells. This phenomenon took place predominantly at concentration of 50 µg/mL.
  
  
  CONCLUSIONS
  The results showed potent stimulation of the proliferative response of PBMC by bovine lactoferrin, associated with the induction of proinflammatory cytokines only in the case of colostral bLF. This observation may be of importance when high doses of bLF are used in therapy and by designing diet supplementation with this protein.
authors.affiliation: Laboratory of Immunobiology, Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wrocław, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Zaczyńska
authors.affiliation: Laboratory of Immunobiology, Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wrocław, Poland.
authors.forename: Maja
authors.initials: M
authors.lastname: Kocięba
authors.affiliation: Laboratory of Immunobiology, Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wrocław, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Śliwińska
authors.affiliation: Laboratory of Immunobiology, Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wrocław, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Zimecki
mesh_terms: D000818:Animals; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003126:Colostrum / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D007781:Lactoferrin / Q000302:isolation & purification / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D008892:Milk / Q000737:chemistry; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007781:Lactoferrin